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2000
Volume 21, Issue 4
  • ISSN: 1573-3947
  • E-ISSN: 1875-6301

Abstract

The skin is the body's largest organ and serves as a barrier against hazardous substances and external attacks. The repeated exposure to these external factors like UV radiation, chemical irritants, pollution, smoke, , increases the skin cancer risk. In the United States, skin cancer is a serious health issue. There is a lack of medications that can effectively treat skin malignancies. Additionally, the current medications have a range of harmful side effects. Consequently, there is an immediate need for skin cancer treatments that have fewer negative effects. The preventative potential, therapeutic benefits, bioavailability, and structure-activity relationship of some chosen phytochemicals for the treatment of skin cancer are discussed in the review. Many cancer treatments have originated from marine sources, bacteria and even plants. Cutaneous malignant melanoma has the highest death rate of all skin cancers and is the most aggressive type of the disease. There are several ways to treat malignant melanoma; however, they all have very poor success rates because of the emergence of multi-drug resistance. Phytochemicals are an alternate therapy approach that is both easily accessible and affordable. Plant-derived phytoconstituents offer a promising anti-carcinogenic potential for tumors connected to the skin because of their widespread acceptability, safety, fewer side effects, and signal transmission routes that can be targeted in more than one way. Skin malignancies are a substantial cause of morbidity and death in the modern world, and research on novel phytochemicals for their potential to prevent and treat skin cancers has increased dramatically as a result. The antitumor effect of plant-derived medicinal substances can be attributed to several different mechanisms and routes, including the breakdown of mitochondrial membrane potential. This review aimed to provide a concise overview of naturally occurring chemical compounds that are currently utilized in cancer chemotherapies or have demonstrated potential in avoiding melanoma or skin cancer. The overview encompasses a variety of phytochemicals, such as flavonoids, carotenoids, terpenoids, selected polyphenols, and crude plant extracts.

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References

  1. ErbP. JiJ. WernliM. KumpE. GlaserA. BüchnerS.A. Role of apoptosis in basal cell and squamous cell carcinoma formation.Immunol. Lett.20051001687210.1016/j.imlet.2005.06.008 16054233
     [Google Scholar]
  2. GreenD.R. Apoptosis: Physiology and pathology.Cambridge, EnglandCambridge University Press2011
     [Google Scholar]
  3. KuppusamyP. YusoffM.M. ManiamG.P. GovindanN. A case study–regulation and functional mechanisms of cancer cells and control their activity using plants and their derivatives.J. Pharm. Res.201368884892
     [Google Scholar]
  4. CammarotaG. IaniroG. AhernA. Gut microbiome, big data and machine learning to promote precision medicine for cancer.Nat. Rev. Gastroenterol. Hepatol.2020171063564810.1038/s41575‑020‑0327‑3 32647386
     [Google Scholar]
  5. KushiL.H. DoyleC. McCulloughM. American Cancer Society guidelines on nutrition and physical activity for cancer prevention.CA Cancer J. Clin.2012621306710.3322/caac.20140 22237782
     [Google Scholar]
  6. CzarneckaA.M. BartnikE. FiedorowiczM. RutkowskiP. Targeted therapy in melanoma and mechanisms of resistance.Int. J. Mol. Sci.20202113457610.3390/ijms21134576
     [Google Scholar]
  7. CristiniV. LowengrubJ. Multiscale modeling of cancer: An integrated experimental and mathematical modeling approach.Cambridge, EnglandCambridge University Press201010.1017/CBO9780511781452
     [Google Scholar]
  8. KhazirJ. MirB.A. PilcherL. RileyD.L. Role of plants in anticancer drug discovery.Phytochem. Lett.2014717318110.1016/j.phytol.2013.11.010
     [Google Scholar]
  9. AnastyukS.D. ShevchenkoN.M. ErmakovaS.P. Anticancer activity in vitro of a fucoidan from the brown alga Fucus evanescens and its low-molecular fragments, structurally characterized by tandem mass-spectrometry.Carbohydr. Polym.201287118619410.1016/j.carbpol.2011.07.036 34662949
     [Google Scholar]
  10. KrólS. KiełbusM. Rivero-MüllerA. StepulakA. Comprehensive review on betulin as a potent anticancer agent.BioMed Res. Int.2015201558418910.1155/2015/584189
     [Google Scholar]
  11. BrohemC.A. da Silva CardealL.B. TiagoM. SoengasM.S. de Moraes BarrosS.B. Maria-EnglerS.S. Artificial skin in perspective: Concepts and applications.Pigment Cell Melanoma Res.2011241355010.1111/j.1755‑148X.2010.00786.x 21029393
     [Google Scholar]
  12. MetcalfeA.D. FergusonM.W.J. Tissue engineering of replacement skin: The crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration.J. R. Soc. Interface200741441343710.1098/rsif.2006.0179 17251138
     [Google Scholar]
  13. ChioniA.M. GroseR. Organotypic modelling as a means of investigating epithelial-stromal interactions during tumourigenesis.Fibrogenesis Tissue Repair200811810.1186/1755‑1536‑1‑8 19014647
     [Google Scholar]
  14. RaaschB. Management of superficial basal cell carcinoma: Focus on imiquimod.Clin. Cosmet. Investig. Dermatol.20092657510.2147/CCID.S3507 21436969
     [Google Scholar]
  15. SweetmanS.C. BlakeP.S. Martindale: The complete drug reference. 37th ed.J Med Libr Assoc20121001756
     [Google Scholar]
  16. AlifrangisC. KoiziaL. RozarioA. The experiences of cancer patients.QJM2011104121075108110.1093/qjmed/hcr129 21835781
     [Google Scholar]
  17. SlevinM.L. StubbsL. PlantH.J. Attitudes to chemotherapy: Comparing views of patients with cancer with those of doctors, nurses, and general public.BMJ199030067371458146010.1136/bmj.300.6737.1458 2379006
     [Google Scholar]
  18. ThorntonM. ParryM. GillP. MeadD. MacbethF. Hard choices: A qualitative study of influences on the treatment decisions made by advanced lung cancer patients.Int. J. Palliat. Nurs.2011172687410.12968/ijpn.2011.17.2.68 21378690
     [Google Scholar]
  19. MolassiotisA. Fernadez-OrtegaP. PudD. Use of complementary and alternative medicine in cancer patients: A European survey.Ann. Oncol.200516465566310.1093/annonc/mdi110 15699021
     [Google Scholar]
  20. CraggG.M. NewmanD.J. Natural products: A continuing source of novel drug leads.Biochim. Biophys. Acta, Gen. Subj.2013183063670369510.1016/j.bbagen.2013.02.008
     [Google Scholar]
  21. HwangS.Y. ChaeJ. KwakA.W. LeeM.H. ShimJ.H. Alternative options for skin cancer therapy via regulation of AKT and related signaling pathways.Int. J. Mol. Sci.20202118686910.3390/ijms21186869
     [Google Scholar]
  22. D’OrazioJ. JarrettS. Amaro-OrtizA. ScottT. UV radiation and the skin.Int. J. Mol. Sci.2013146122221224810.3390/ijms140612222 23749111
     [Google Scholar]
  23. NarayananD.L. SaladiR.N. FoxJ.L. Review: Ultraviolet radiation and skin cancer.Int. J. Dermatol.201049997898610.1111/j.1365‑4632.2010.04474.x 20883261
     [Google Scholar]
  24. GlosterH.M.Jr NealK. Skin cancer in skin of color.J. Am. Acad. Dermatol.200655574176010.1016/j.jaad.2005.08.063 17052479
     [Google Scholar]
  25. LiuG. ChuH. Andrographolide inhibits proliferation and induces cell cycle arrest and apoptosis in human melanoma cells.Oncol. Lett.20181545301530510.3892/ol.2018.7941 29552170
     [Google Scholar]
  26. ZhouC ChenX ZengW Propranolol induced G0/G1/S phase arrest and apoptosis in melanoma cells via AKT/MAPK pathway. Oncotarget2016742683146832742, 68314.10.18632/oncotarget.11599 27582542
  27. SaginalaK. BarsoukA. AluruJ.S. RawlaP. BarsoukA. Epidemiology of Melanoma.Med. Sci. (Basel)2021946310.3390/medsci9040063 34698235
     [Google Scholar]
  28. YahyaY.F. FantoniO.J. BudiamalS. ToruanT.L. Profile of Non-melanoma skin cancer and malignant melanoma at Dr. Mohammad Hoesin General Hospital Palembang from 2017-2019: A retrospective study.Bioscientia Medicina: J Biomed Trans Res2022661896190710.37275/bsm.v6i6.531
     [Google Scholar]
  29. IyerA.K. SinghA. GantaS. AmijiM.M. Role of integrated cancer nanomedicine in overcoming drug resistance.Adv. Drug Deliv. Rev.20136513-141784180210.1016/j.addr.2013.07.012
     [Google Scholar]
  30. KunjachanS. RychlikB. StormG. KiesslingF. LammersT. Multidrug resistance: Physiological principles and nanomedical solutions.Adv. Drug Deliv. Rev.20136513-141852186510.1016/j.addr.2013.09.018
     [Google Scholar]
  31. MarkmanJ.L. RekechenetskiyA. HollerE. LjubimovaJ.Y. Nanomedicine therapeutic approaches to overcome cancer drug resistance.Adv. Drug Deliv. Rev.20136513-141866187910.1016/j.addr.2013.09.019
     [Google Scholar]
  32. FlahertyK.T. PuzanovI. KimK.B. Inhibition of mutated, activated BRAF in metastatic melanoma.N. Engl. J. Med.2010363980981910.1056/NEJMoa1002011 20818844
     [Google Scholar]
  33. SosmanJ.A. KimK.B. SchuchterL. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib.N. Engl. J. Med.2012366870771410.1056/NEJMoa1112302 22356324
     [Google Scholar]
  34. NikolaouV.A. StratigosA.J. FlahertyK.T. TsaoH. Melanoma: New insights and new therapies.J. Invest. Dermatol.2012132385486310.1038/jid.2011.421 22217739
     [Google Scholar]
  35. FlahertyK.T. Targeting metastatic melanoma.Annu. Rev. Med.201263117118310.1146/annurev‑med‑050410‑105655 22034865
     [Google Scholar]
  36. JiZ. FlahertyK.T. TsaoH. Targeting the RAS pathway in melanoma.Trends Mol. Med.2012181273510.1016/j.molmed.2011.08.001 21962474
     [Google Scholar]
  37. HodiF.S. ObleD.A. DrappatzJ. CTLA-4 blockade with ipilimumab induces significant clinical benefit in a female with melanoma metastases to the CNS.Nat. Clin. Pract. Oncol.20085955756110.1038/ncponc1183 18665147
     [Google Scholar]
  38. HodiF.S. O’DayS.J. McDermottD.F. Improved survival with ipilimumab in patients with metastatic melanoma.N. Engl. J. Med.2010363871172310.1056/NEJMoa1003466 20525992
     [Google Scholar]
  39. Suarez-RodriguezB. Lopez-AbenteG. MartínezC. Occupation and skin cancer: The results of the HELIOS-I multicenter case-control study.BMC Public Health2007718010.1186/1471‑2458‑7‑180
     [Google Scholar]
  40. RheeJ.S. MatthewsB.A. NeuburgM. LoganB.R. BurzynskiM. NattingerA.B. The skin cancer index: Clinical responsiveness and predictors of quality of life.Laryngoscope2007117339940510.1097/MLG.0b013e31802e2d88 17334300
     [Google Scholar]
  41. DonaldsonM.R. ColdironB.M. No end in sight: The skin cancer epidemic continues.Semin. Cutan. Med. Surg.20113013510.1016/j.sder.2011.01.002
     [Google Scholar]
  42. WHO Ultraviolet radiation.2022Available From: https://www.who.int/news-room/fact-sheets/detail/ultraviolet-radiation
    [Google Scholar]
  43. BoyleP DoréJF AutierP RingborgU Cancer of the skin: A forgotten problem in Europe. Ann Oncol20041515610.1093/annonc/mdh03214679111
     [Google Scholar]
  44. RittiéL. KansraS. StollS.W. Differential ErbB1 signaling in squamous cell versus basal cell carcinoma of the skin.Am. J. Pathol.200717062089209910.2353/ajpath.2007.060537 17525275
     [Google Scholar]
  45. O’DriscollL. McMorrowJ. DoolanP. Investigation of the molecular profile of basal cell carcinoma using whole genome microarrays.Mol. Cancer2006517410.1186/1476‑4598‑5‑74 17173689
     [Google Scholar]
  46. KuttanG. PratheeshkumarP. ManuK.A. KuttanR. Inhibition of tumor progression by naturally occurring terpenoids.Pharm. Biol.20114910995100710.3109/13880209.2011.559476 21936626
     [Google Scholar]
  47. SteinmetzK.A. PotterJ.D. Vegetables, fruit, and cancer. II. Mechanisms.Cancer Causes Control19912642744210.1007/BF00054304 1764568
     [Google Scholar]
  48. HendricksonJ.B. The molecules of nature: A survey of the biosynthesis and chemistry of natural products.United StatesW. A. Benjamin Advanced Book Program1973
     [Google Scholar]
  49. CorcoranM.P. McKayD.L. BlumbergJ.B. Flavonoid basics: Chemistry, sources, mechanisms of action, and safety.J. Nutr. Gerontol. Geriatr.201231317618910.1080/21551197.2012.698219 22888837
     [Google Scholar]
  50. GlosterH.M.Jr BrodlandD.G. The epidemiology of skin cancer.Dermatol. Surg.199622321722610.1111/j.1524‑4725.1996.tb00312.x 8599733
     [Google Scholar]
  51. SaeidniaS. AbdollahiM. Antioxidants: Friends or foe in prevention or treatment of cancer: The debate of the century.Toxicol. Appl. Pharmacol.20132711496310.1016/j.taap.2013.05.004 23680455
     [Google Scholar]
  52. KachuriL. DeP. EllisonL.F. SemenciwR. Cancer incidence, mortality and survival trends in Canada, 1970–2007.Chronic Dis. Inj. Can.2013332698010.24095/hpcdp.33.2.03 23470172
     [Google Scholar]
  53. CaoW. ChenH.D. YuY.W. LiN. ChenW.Q. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020.Chin. Med. J. (Engl.)2021134778379110.1097/CM9.0000000000001474 33734139
     [Google Scholar]
  54. CraggG.M. GrothausP.G. NewmanD.J. Impact of natural products on developing new anti-cancer agents.Chem. Rev.200910973012304310.1021/cr900019j 19422222
     [Google Scholar]
  55. RigelD.S. Epidemiology of melanoma.Semin. Cutan. Med. Surg.201029420420910.1016/j.sder.2010.10.005
     [Google Scholar]
  56. FranceschiS. CristofoliniM. Cutaneous malignant melanoma: Epidemiological considerations.Semin. Surg. Oncol.19928634535210.1002/ssu.2980080603
     [Google Scholar]
  57. RiversJ.K. The detection and management of dysplastic nevi and early melanoma.World J. Surg.199216216617210.1007/BF02071516 1561795
     [Google Scholar]
  58. GarlandC.F. GarlandF.C. GorhamE.D. Rising trends in melanoma an hypothesis concerning sunscreen effectiveness.Ann. Epidemiol.19933110311010.1016/1047‑2797(93)90017‑X 8287144
     [Google Scholar]
  59. MarkovicS.N. EricksonL.A. RaoR.D. Malignant melanoma in the 21st century, part 1: Epidemiology, risk factors, screening, prevention, and diagnosis.Mayo Clin. Proc.200782336438010.1016/S0025‑6196(11)61033‑1 17352373
     [Google Scholar]
  60. BrochezL. NaeyaertJ.M. Understanding the trends in melanoma incidence and mortality: Where do we stand?Eur. J. Dermatol.20001017175 10694303
     [Google Scholar]
  61. DiepgenT.L. MahlerV. The epidemiology of skin cancer.Br. J. Dermatol.2002146S611610.1046/j.1365‑2133.146.s61.2.x 11966724
     [Google Scholar]
  62. MullikenJ.S. RussakJ.E. RigelD.S. The effect of sunscreen on melanoma risk.Dermatol. Clin.201230336937610.1016/j.det.2012.04.002 22800545
     [Google Scholar]
  63. SaladiR.N. PersaudA.N. The causes of skin cancer: A comprehensive review.Drugs Today (Barc)2005411375310.1358/dot.2005.41.1.875777 15753968
     [Google Scholar]
  64. LeiterU. GarbeC. Epidemiology of melanoma and nonmelanoma skin cancer-the role of sunlight.Adv. Exp. Med. Biol.200862489103
     [Google Scholar]
  65. NorvalM. LucasR.M. CullenA.P. The human health effects of ozone depletion and interactions with climate change.Photochem. Photobiol. Sci.201110219922510.1039/c0pp90044c 21253670
     [Google Scholar]
  66. NikolaouV. StratigosA.J. Emerging trends in the epidemiology of melanoma.Br. J. Dermatol.20141701111910.1111/bjd.12492 23815297
     [Google Scholar]
  67. WeinstockM.A. Cutaneous melanoma: Public health approach to early detection.Dermatol. Ther.2006191263110.1111/j.1529‑8019.2005.00053.x 16405567
     [Google Scholar]
  68. GordonR. Skin cancer: An overview of epidemiology and risk factors.Semin. Oncol. Nurs.201329316016910.1016/j.soncn.2013.06.002
     [Google Scholar]
  69. GrantW.B. MoanJ. ReichrathJ. Comment on “the effects on human health from stratospheric ozone depletion and its interactions with climate change” by M. Norval, A. P. Cullen, F. R. de Gruijl, J. Longstreth, Y. Takizawa, R. M. Lucas, F. P. Noonan and J. C. van der Leu, Photochem. Photobiol. Sci., 2007, 6, 232.Photochem. Photobiol. Sci.20076891291510.1039/b705482c 17668123
     [Google Scholar]
  70. NorvalM. CullenA.P. de GruijlF.R. The effects on human health from stratospheric ozone depletion and its interactions with climate change.Photochem. Photobiol. Sci.20076323225110.1039/b700018a 17344960
     [Google Scholar]
  71. MadanV. LearJ.T. SzeimiesR.M. Non-melanoma skin cancer.Lancet2010375971567368510.1016/S0140‑6736(09)61196‑X 20171403
     [Google Scholar]
  72. LomasA. Leonardi-BeeJ. Bath-HextallF. A systematic review of worldwide incidence of nonmelanoma skin cancer.Br. J. Dermatol.201216651069108010.1111/j.1365‑2133.2012.10830.x 22251204
     [Google Scholar]
  73. CainiS. GandiniS. SeraF. Meta-analysis of risk factors for cutaneous melanoma according to anatomical site and clinico-pathological variant.Eur. J. Cancer200945173054306310.1016/j.ejca.2009.05.009 19545997
     [Google Scholar]
  74. GandiniS. SeraF. CattaruzzaM.S. Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure.Eur. J. Cancer2005411456010.1016/j.ejca.2004.10.016 15617990
     [Google Scholar]
  75. WhitemanD. GreenA. Epidemiology of Malignant Melanoma.Skin Cancer - A World-Wide Perspective.United StatesSpringerLink2011
     [Google Scholar]
  76. Togsverd-BoK. SørensenS.S. HædersdalM. Organ transplant recipients need intensive control and treatment of skin cancerUgeskr. Laeger20131752014081411 23663395
     [Google Scholar]
  77. SuV.Y.F. HuY.W. ChouK.T. Amiodarone and the risk of cancer.Cancer201311991699170510.1002/cncr.27881 23568847
     [Google Scholar]
  78. ThinnesF.P. Nonmelanoma skin cancer is associated with reduced Alzheimer disease risk.Neurology201380211966197210.1212/01.wnl.0000436924.94798.59
     [Google Scholar]
  79. GaliczynskiE.M. VidimosA.T. Nonsurgical treatment of nonmelanoma skin cancer.Dermatol. Clin.201129229730910.1016/j.det.2011.01.01121421153
     [Google Scholar]
  80. ClarkeP. Nonmelanoma skin cancers - treatment options.Aust. Fam. Physician2012417476480 22762065
     [Google Scholar]
  81. LazarethV. Management of non-melanoma skin cancer.Semin. Oncol. Nurs.201329318219410.1016/j.soncn.2013.06.004 23958216
     [Google Scholar]
  82. MartinezJ.C. OtleyC.C. The management of melanoma and nonmelanoma skin cancer: A review for the primary care physician.Mayo Clin. Proc.200176121253126510.4065/76.12.1253 11761506
     [Google Scholar]
  83. MoanJ. PengQ. An outline of the hundred-year history of PDT.Anticancer Res.2003235A35913600 14666654
     [Google Scholar]
  84. LevyJ.G. Photosensitizers in photodynamic therapy.Semin. Oncol.1994216Suppl. 15410 7992105
     [Google Scholar]
  85. SzeimiesR.M. LandthalerM. Photodynamic therapy and fluorescence diagnosis of skin cancers.Recent Results Cancer Res.200216024024510.1007/978‑3‑642‑59410‑6_28 12079219
     [Google Scholar]
  86. TaubA.F. Photodynamic therapy in dermatology: History and horizons.J. Drugs Dermatol.200431Suppl.S8S25 14964757
     [Google Scholar]
  87. LuiH. Photodynamic therapy in dermatology with porfimer sodium and benzoporphyrin derivative: An update.Semin. Oncol.1994216Suppl. 151114 7992101
     [Google Scholar]
  88. McGillisS.T. FeinH. Topical treatment strategies for non-melanoma skin cancer and precursor lesions.Semin. Cutan. Med. Surg.200423317418310.1016/j.sder.2004.06.005
     [Google Scholar]
  89. AminiS. VieraM.H. ValinsW. BermanB. Nonsurgical innovations in the treatment of nonmelanoma skin cancer.J. Clin. Aesthet. Dermatol.2010362034 20725548
     [Google Scholar]
  90. EricksonC. MillerS.J. Treatment options in melanoma in situ: Topical and radiation therapy, excision and Mohs surgery.Int. J. Dermatol.201049548249110.1111/j.1365‑4632.2010.04423.x 20534080
     [Google Scholar]
  91. HoelderS. ClarkeP.A. WorkmanP. Discovery of small molecule cancer drugs: Successes, challenges and opportunities.Mol. Oncol.20126215517610.1016/j.molonc.2012.02.004 22440008
     [Google Scholar]
  92. ChakrabortyR. WielandC.N. ComfereN.I. Molecular targeted therapies in metastatic melanoma.Pharm. Genomics Pers. Med.201364956 23843700
     [Google Scholar]
  93. KievitF.M. ZhangM. Cancer nanotheranostics: Improving imaging and therapy by targeted delivery across biological barriers.Adv. Mater.20112336H217H24710.1002/adma.201102313 21842473
     [Google Scholar]
  94. FineganK.G. TournierC. The mitogen-activated protein kinase kinase 4 has a pro-oncogenic role in skin cancer.Cancer Res.201070145797580610.1158/0008‑5472.CAN‑09‑3669 20610622
     [Google Scholar]
  95. FongZ.V. TanabeK.K. Comparison of melanoma guidelines in the U.S.A., Canada, Europe, Australia and New Zealand: A critical appraisal and comprehensive review.Br. J. Dermatol.20141701203010.1111/bjd.12687 24116870
     [Google Scholar]
  96. YapT.A. WorkmanP. Exploiting the cancer genome: Strategies for the discovery and clinical development of targeted molecular therapeutics.Annu. Rev. Pharmacol. Toxicol.201252154957310.1146/annurev‑pharmtox‑010611‑134532 22235862
     [Google Scholar]
  97. de BonoJ.S. AshworthA. Translating cancer research into targeted therapeutics.Nature2010467731554354910.1038/nature09339 20882008
     [Google Scholar]
  98. KatiyarS.K. Green tea prevents non-melanoma skin cancer by enhancing DNA repair.Arch. Biochem. Biophys.2011508215215810.1016/j.abb.2010.11.015 21094124
     [Google Scholar]
  99. Van WykB. van OudtshoornB. GerickeN. Medicinal Plants of South Africa.1st edPretoria, South AfricaBriza Publications1997130410.1016/j.sajb.2011.08.011
     [Google Scholar]
  100. CraggG.M. NewmanD.J. Plants as a source of anti-cancer agents.J. Ethnopharmacol.20051001-2727910.1016/j.jep.2005.05.011 16009521
     [Google Scholar]
  101. NobiliS. LippiD. WitortE. Natural compounds for cancer treatment and prevention.Pharmacol. Res.200959636537810.1016/j.phrs.2009.01.017 19429468
     [Google Scholar]
  102. WangS. MecklingK.A. MarconeM.F. KakudaY. TsaoR. Can phytochemical antioxidant rich foods act as anti-cancer agents?Food Res. Int.20114492545255410.1016/j.foodres.2011.05.021
     [Google Scholar]
  103. BatraP. SharmaA.K. Anti-cancer potential of flavonoids: Recent trends and future perspectives.Molecules2014191170810.1007/s13205‑013‑0117‑5
     [Google Scholar]
  104. ParkK.K. ChunK.S. LeeJ.M. LeeS.S. SurhY.J. Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice.Cancer Lett.1998129213914410.1016/S0304‑3835(98)00081‑0 9719454
     [Google Scholar]
  105. KimS.O. ChunK.S. KunduJ.K. SurhY.J. Inhibitory effects of [6]‐gingerol on PMA‐induced COX‐2 expression and activation of NF‐κB and p38 MAPK in mouse skin.Biofactors2004211-4273110.1002/biof.552210107 15630166
     [Google Scholar]
  106. KimJ.K. KimY. NaK.M. SurhY.J. KimT.Y. [6]-Gingerol prevents UVB-induced ROS production and COX-2 expression in vitro and in vivo.Free Radic. Res.200741560361410.1080/10715760701209896 17454143
     [Google Scholar]
  107. BodeA.M. MaW-Y. SurhY-J. DongZ. Inhibition of epidermal growth factor-induced cell transformation and activator protein 1 activation by [6]-gingerol.Cancer Res.2001613850853 11221868
     [Google Scholar]
  108. NigamN. GeorgeJ. SrivastavaS. RETRACTED ARTICLE: Induction of apoptosis by [6]-gingerol associated with the modulation of p53 and involvement of mitochondrial signaling pathway in B[a]P-induced mouse skin tumorigenesis.Cancer Chemother. Pharmacol.201065468769610.1007/s00280‑009‑1074‑x 19629484
     [Google Scholar]
  109. RatcharinN WongtrakulP IndranupakornR. Preparation of Zingiber officinale extract loaded solid lipid nanoparticles.AMR2012506389910.4028/www.scientific.net/amr.506.389
     [Google Scholar]
  110. XiangD. WangD. HeY. Caffeic acid phenethyl ester induces growth arrest and apoptosis of colon cancer cells via the β-catenin/T-cell factor signaling.Anticancer Drugs200617775376210.1097/01.cad.0000224441.01082.bb 16926625
     [Google Scholar]
  111. ChenM.F. WuC.T. ChenY.J. KengP.C. ChenW.C. Cell killing and radiosensitization by caffeic acid phenethyl ester (CAPE) in lung cancer cells.J. Radiat. Res.200445225326010.1269/jrr.45.253 15304968
     [Google Scholar]
  112. KuduguntiS.K. VadN.M. EkogboE. MoridaniM.Y. Efficacy of Caffeic Acid Phenethyl Ester (CAPE) in skin B16-F0 melanoma tumor bearing C57BL/6 mice.Invest. New Drugs2011291526210.1007/s10637‑009‑9334‑5 19844662
     [Google Scholar]
  113. KuoH.C. KuoW.H. LeeY.J. LinW.L. ChouF.P. TsengT.H. Inhibitory effect of caffeic acid phenethyl ester on the growth of C6 glioma cells in vitro and in vivo.Cancer Lett.2006234219920810.1016/j.canlet.2005.03.046 15885897
     [Google Scholar]
  114. ChenM.J. ChangW.H. LinC.C. Caffeic acid phenethyl ester induces apoptosis of human pancreatic cancer cells involving caspase and mitochondrial dysfunction.Pancreatology20088655856510.1159/000159214 18824880
     [Google Scholar]
  115. WuC-S. ChenM-F. LeeI-L. TungS-Y. Predictive role of nuclear factor-kappaB activity in gastric cancer: A promising adjuvant approach with caffeic acid phenethyl ester.J. Clin. Gastroenterol.2007411089490010.1097/MCG.0b013e31804c707c 18090157
     [Google Scholar]
  116. OnoriP. DeMorrowS. GaudioE. Caffeic acid phenethyl ester decreases cholangiocarcinoma growth by inhibition of NF‐κB and induction of apoptosis.Int. J. Cancer2009125356557610.1002/ijc.24271 19358267
     [Google Scholar]
  117. LeeK.W. KangN.J. KimJ.H. Caffeic acid phenethyl ester inhibits invasion and expression of matrix metalloproteinase in SK-Hep1 human hepatocellular carcinoma cells by targeting nuclear factor kappa B.Genes Nutr.20082431932210.1007/s12263‑007‑0067‑9 18850224
     [Google Scholar]
  118. WuJ. HortonL. BoslandM. KarkoszkaJ. FrenkelK. Caffeic acid phenethyl ester (CAPE) as a preventive agent in a preclinical model of breast cancer.Cancer Res.20076791418
     [Google Scholar]
  119. NatarajanK. SinghS. BurkeT.R.Jr GrunbergerD. AggarwalB.B. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-κ B.Proc. Natl. Acad. Sci. USA199693179090909510.1073/pnas.93.17.9090 8799159
     [Google Scholar]
  120. WuJ. OmeneC. KarkoszkaJ. Caffeic acid phenethyl ester (CAPE), derived from a honeybee product propolis, exhibits a diversity of anti-tumor effects in pre-clinical models of human breast cancer.Cancer Lett.20113081435310.1016/j.canlet.2011.04.012 21570765
     [Google Scholar]
  121. ChenY.J. ShiaoM.S. HsuM.L. TsaiT.H. WangS.Y. Effect of caffeic acid phenethyl ester, an antioxidant from propolis, on inducing apoptosis in human leukemic HL-60 cells.J. Agric. Food Chem.200149115615561910.1021/jf0107252 11714368
     [Google Scholar]
  122. FrenkelK. WeiH. BhimaniR. Inhibition of tumor promoter-mediated processes in mouse skin and bovine lens by caffeic acid phenethyl ester.Cancer Res.199353612551261 7680281
     [Google Scholar]
  123. GuptaS.C. PatchvaS. AggarwalB.B. Therapeutic roles of curcumin: Lessons learned from clinical trials.AAPS J.201315119521810.1208/s12248‑012‑9432‑8 23143785
     [Google Scholar]
  124. KuttanR. SudheeranP.C. JosphC.D. Turmeric and curcumin as topical agents in cancer therapy.Tumori1987731293110.1177/030089168707300105 2435036
     [Google Scholar]
  125. DahmkeI.N. BackesC. Rudzitis-AuthJ. Curcumin intake affects miRNA signature in murine melanoma with mmu-miR-205-5p most significantly altered.PLoS One2013812e8112210.1371/journal.pone.0081122 24349037
     [Google Scholar]
  126. GuptaS.C. PatchvaS. KohW. AggarwalB.B. Discovery of curcumin, a component of golden spice, and its miraculous biological activities.Clin. Exp. Pharmacol. Physiol.201239328329910.1111/j.1440‑1681.2011.05648.x 22118895
     [Google Scholar]
  127. SukumaranK. UnnikrishnanM.C. KuttanR. Inhibition of tumour promotion in mice by eugenol.Indian J. Physiol. Pharmacol.1994384306308 7883300
     [Google Scholar]
  128. KaurG. AtharM. AlamM.S. Eugenol precludes cutaneous chemical carcinogenesis in mouse by preventing oxidative stress and inflammation and by inducing apoptosis.Mol. Carcinog.201049329030110.1002/mc.20601 20043298
     [Google Scholar]
  129. GhoshR. NadimintyN. FitzpatrickJ.E. AlworthW.L. SlagaT.J. KumarA.P. Eugenol causes melanoma growth suppression through inhibition of E2F1 transcriptional activity.J. Biol. Chem.200528075812581910.1074/jbc.M411429200 15574415
     [Google Scholar]
  130. PalD. BanerjeeS. MukherjeeS. RoyA. PandaC.K. DasS. Eugenol restricts DMBA croton oil induced skin carcinogenesis in mice: Downregulation of c-Myc and H-ras, and activation of p53 dependent apoptotic pathway.J. Dermatol. Sci.2010591313910.1016/j.jdermsci.2010.04.013 20537511
     [Google Scholar]
  131. EsmaeiliF. RajabnejhadS. PartoazarA.R. Anti-inflammatory effects of eugenol nanoemulsion as a topical delivery system.Pharm. Dev. Technol.201621788789310.3109/10837450.2015.1078353 26365132
     [Google Scholar]
  132. FernándezM.A. SáenzM.T. GarcíaM.D. Anti-inflammatory activity in rats and mice of phenolic acids isolated from Scrophularia frutescens.J. Pharm. Pharmacol.201150101183118610.1111/j.2042‑7158.1998.tb03332.x 9821668
     [Google Scholar]
  133. MoonM.K. LeeY.J. KimJ.S. KangD.G. LeeH.S. Effect of caffeic acid on tumor necrosis factor-α-induced vascular inflammation in human umbilical vein endothelial cells.Biol. Pharm. Bull.20093281371137710.1248/bpb.32.1371 19652376
     [Google Scholar]
  134. TsaiS. ChaoC. YinM. Preventive and therapeutic effects of caffeic acid against inflammatory injury in striatum of MPTP-treated mice.Eur. J. Pharmacol.20116702-344144710.1016/j.ejphar.2011.09.171 21970803
     [Google Scholar]
  135. KangN.J. LeeK.W. KimB.H. Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK.Carcinogenesis201132692192810.1093/carcin/bgr022 21317303
     [Google Scholar]
  136. JungJ.E. KimH.S. LeeC.S. Caffeic acid and its synthetic derivative CADPE suppress tumor angiogenesis by blocking STAT3-mediated VEGF expression in human renal carcinoma cells.Carcinogenesis20072881780178710.1093/carcin/bgm130 17557905
     [Google Scholar]
  137. YangY. LiY. WangK. WangY. YinW. LiL. P38/NF-κB/snail pathway is involved in caffeic acid-induced inhibition of cancer stem cells-like properties and migratory capacity in malignant human keratinocyte.PLoS One201383e5891510.1371/journal.pone.0058915 23516577
     [Google Scholar]
  138. McCubreyJ.A. SteelmanL.S. ChappellW.H. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance.Biochim. Biophys. Acta Mol. Cell Res.2007177381263128410.1016/j.bbamcr.2006.10.001 17126425
     [Google Scholar]
  139. KangN.J. LeeK.W. ShinB.J. Caffeic acid, a phenolic phytochemical in coffee, directly inhibits Fyn kinase activity and UVB-induced COX-2 expression.Carcinogenesis200830232133010.1093/carcin/bgn282 19073879
     [Google Scholar]
  140. SinghM. SumanS. ShuklaY. New enlightenment of skin cancer chemoprevention through phytochemicals: In vitro and in vivo studies and the underlying mechanisms.BioMed Res. Int.2014201411810.1155/2014/243452 24757666
     [Google Scholar]
  141. WeiH. SaladiR. LuY. Isoflavone genistein: Photoprotection and clinical implications in dermatology.J. Nutr.200313311Suppl. 13811S3819S10.1093/jn/133.11.3811S 14608119
     [Google Scholar]
  142. RusinA. KrawczykZ. GrynkiewiczG. GoglerA. Zawisza-PuchałkaJ. SzejaW. Synthetic derivatives of genistein, their properties and possible applications.Acta Biochim. Pol.2010571233410.18388/abp.2010_2368 20216977
     [Google Scholar]
  143. WeiH. BowenR. ZhangX. LebwohlM. Isoflavone genistein inhibits the initiation and promotion of two-stage skin carcinogenesis in mice.Carcinogenesis19981981509151410.1093/carcin/19.8.1509 9744550
     [Google Scholar]
  144. SarkarF.H. LiY. Mechanisms of cancer chemoprevention by soy isoflavone genistein.Cancer Metastasis Rev.2002213/426528010.1023/A:1021210910821 12549765
     [Google Scholar]
  145. LiQ.S. LiC.Y. LiZ.L. ZhuH.L. Genistein and its synthetic analogs as anticancer agents.Anticancer. Agents Med. Chem.201212327128110.2174/187152012800228788 22043996
     [Google Scholar]
  146. López-LázaroM. Distribution and biological activities of the flavonoid luteolin.Mini Rev. Med. Chem.200991315910.2174/138955709787001712 19149659
     [Google Scholar]
  147. HoribeI. SatohY. ShiotaY. Induction of melanogenesis by 4′-O-methylated flavonoids in B16F10 melanoma cells.J. Nat. Med.201367470571010.1007/s11418‑012‑0727‑y 23208771
     [Google Scholar]
  148. HorváthováK. ChalupaI. ŠebováL. TóthováD. VachálkováA. Protective effect of quercetin and luteolin in human melanoma HMB-2 cells.Mutat. Res. Genet. Toxicol. Environ. Mutagen.2005565210511210.1016/j.mrgentox.2004.08.013 15661608
     [Google Scholar]
  149. IwashitaK. KoboriM. YamakiK. TsushidaT. Flavonoids inhibit cell growth and induce apoptosis in B16 melanoma 4A5 cells.Biosci. Biotechnol. Biochem.20006491813182010.1271/bbb.64.1813 11055382
     [Google Scholar]
  150. NakashimaS. MatsudaH. OdaY. NakamuraS. XuF. YoshikawaM. Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.Bioorg. Med. Chem.20101862337234510.1016/j.bmc.2010.01.046 20189399
     [Google Scholar]
  151. KatiyarS.K. AgarwalR. WoodG.S. MukhtarH. Inhibition of 12-O-tetradecanoylphorbol-13-acetate-caused tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated SENCAR mouse skin by a polyphenolic fraction isolated from green tea.Cancer Res.1992522468906897 1458478
     [Google Scholar]
  152. KatiyarS.K. AfaqF. PerezA. MukhtarH. Green tea polyphenol (-)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress.Carcinogenesis200122228729410.1093/carcin/22.2.287 11181450
     [Google Scholar]
  153. KatiyarS.K. AfaqF. AzizuddinK. MukhtarH. Inhibition of UVB-induced oxidative stress-mediated phosphorylation of mitogen-activated protein kinase signaling pathways in cultured human epidermal keratinocytes by green tea polyphenol (−)-epigallocatechin-3-gallate.Toxicol. Appl. Pharmacol.2001176110117
     [Google Scholar]
  154. AhmadN. GuptaS. MukhtarH. Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor kappaB in cancer cells versus normal cells.Arch. Biochem. Biophys.2000376233834610.1006/abbi.2000.1742 10775421
     [Google Scholar]
  155. DongZ. MaW. HuangC. YangC.S. Inhibition of tumor promoter-induced activator protein 1 activation and cell transformation by tea polyphenols, (-)-epigallocatechin gallate, and theaflavins.Cancer Res.1997571944144419 9331105
     [Google Scholar]
  156. JangM. CaiL. UdeaniG.O. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.Science1997275529721822010.1126/science.275.5297.218 8985016
     [Google Scholar]
  157. AzizM.H. Reagan-ShawS. WuJ. LongleyB.J. AhmadN. Chemoprevention of skin cancer by grape constituent resveratrol: Relevance to human disease?FASEB J.20051991193119510.1096/fj.04‑3582fje 15837718
     [Google Scholar]
  158. NdiayeM. PhilippeC. MukhtarH. AhmadN. The grape antioxidant resveratrol for skin disorders: Promise, prospects, and challenges.Arch. Biochem. Biophys.2011508216417010.1016/j.abb.2010.12.030 21215251
     [Google Scholar]
  159. KowalczykM.C. WalaszekZ. KowalczykP. KinjoT. HanausekM. SlagaT.J. Differential effects of several phytochemicals and their derivatives on murine keratinocytes in vitro and in vivo: Implications for skin cancer prevention.Carcinogenesis20093061008101510.1093/carcin/bgp069 19329757
     [Google Scholar]
  160. JagdeoJ. AdamsL. Lev-TovH. SieminskaJ. MichlJ. BrodyN. Dose-dependent antioxidant function of resveratrol demonstrated via modulation of reactive oxygen species in normal human skin fibroblasts in vitro.J. Drugs Dermatol.201091215231526 21120261
     [Google Scholar]
  161. TokudaH. OhigashiH. KoshimizuK. ItoY. Inhibitory effects of ursolic and oleanolic ancid on skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate.Cancer Lett.198633327928510.1016/0304‑3835(86)90067‑4 3802058
     [Google Scholar]
  162. HuangM-T. HoC-T. WangZ.Y. Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid.Cancer Res.1994543701708 8306331
     [Google Scholar]
  163. Es-saadyD. SimonA. OllierM. MaurizisJ.C. ChuliaA.J. DelageC. Inhibitory effect of ursolic acid on B16 proliferation through cell cycle arrest.Cancer Lett.1996106219319710.1016/0304‑3835(96)04312‑1 8844972
     [Google Scholar]
  164. HarmandP.O. DuvalR. LiagreB. Ursolic acid induces apoptosis through caspase-3 activation and cell cycle arrest in HaCat cells.Int. J. Oncol.200323110511210.3892/ijo.23.1.105 12792782
     [Google Scholar]
  165. ShishodiaS. MajumdarS. BanerjeeS. AggarwalB.B. Ursolic acid inhibits nuclear factor-κB activation induced by carcinogenic agents through suppression of IκBα kinase and p65 phosphorylation.Cancer Res.20036343754383 12907607
     [Google Scholar]
  166. HarmandP.O. DuvalR. DelageC. SimonA. Ursolic acid induces apoptosis through mitochondrial intrinsic pathway and caspase-3 activation in M4Beu melanoma cells.Int. J. Cancer2005114111110.1002/ijc.20588 15523687
     [Google Scholar]
  167. BelmanS. Onion and garlic oils inhibit tumor promotion.Carcinogenesis1983481063106510.1093/carcin/4.8.1063 6872151
     [Google Scholar]
  168. AtharM. RazaH. BickersD.R. MukhtarH. Inhibition of benzoyl peroxide-mediated tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated skin of Sencar mice by antioxidants nordihydroguaiaretic acid and diallyl sulfide.J. Invest. Dermatol.199094216216510.1111/1523‑1747.ep12874431 2105358
     [Google Scholar]
  169. DwivediC. RohlfsS. JarvisD. EngineerF.N. Chemoprevention of chemically induced skin tumor development by diallyl sulfide and diallyl disulfide.Pharm. Res.19929121668167010.1023/A:1015845315500 1488416
     [Google Scholar]
  170. SinghA. ShuklaY. Antitumor activity of diallyl sulfide in two-stage mouse skin model of carcinogenesis.Biomed. Environ. Sci.1998113258263 9861485
     [Google Scholar]
  171. NigamN. BhuiK. PrasadS. GeorgeJ. ShuklaY. [6]-Gingerol induces reactive oxygen species regulated mitochondrial cell death pathway in human epidermoid carcinoma A431 cells.Chem. Biol. Interact.20091811778410.1016/j.cbi.2009.05.012 19481070
     [Google Scholar]
  172. JungS.K. KimJ.E. LeeS.Y. The P110 subunit of PI3-K is a therapeutic target of acacetin in skin cancer.Carcinogenesis201435112313010.1093/carcin/bgt266 23913940
     [Google Scholar]
  173. NihalM. AhmadN. MukhtarH. WoodG.S. Anti‐proliferative and proapoptotic effects of (−)‐epigallocatechin‐3‐gallate on human melanoma: Possible implications for the chemoprevention of melanoma.Int. J. Cancer2005114451352110.1002/ijc.20785 15609335
     [Google Scholar]
  174. DasS. DasJ. PaulA. SamadderA. Khuda-BukhshA.R. Apigenin, a bioactive flavonoid from Lycopodium clavatum, stimulates nucleotide excision repair genes to protect skin keratinocytes from ultraviolet B-induced reactive oxygen species and DNA damage.J. Acupunct. Meridian Stud.20136525226210.1016/j.jams.2013.07.002 24139463
     [Google Scholar]
  175. SyedD.N. AfaqF. MaddodiN. Inhibition of human melanoma cell growth by the dietary flavonoid fisetin is associated with disruption of Wnt/β-catenin signaling and decreased Mitf levels.J. Invest. Dermatol.201113161291129910.1038/jid.2011.6 21346776
     [Google Scholar]
  176. ZhangW. LanY. HuangQ. HuaZ. Galangin induces B16F10 melanoma cell apoptosis via mitochondrial pathway and sustained activation of p38 MAPK.Cytotechnology201365344745510.1007/s10616‑012‑9499‑1 23001390
     [Google Scholar]
  177. BalasubramanianR. NarayananM. KedalgovindaramL. Devarakonda RamaK. Cytotoxic activity of flavone glycoside from the stem of Indigofera aspalathoides Vahl.J. Nat. Med.2006611808310.1007/s11418‑006‑0026‑6
     [Google Scholar]
  178. MassaokaM.H. MatsuoA.L. FigueiredoC.R. Jacaranone induces apoptosis in melanoma cells via ROS-mediated downregulation of Akt and p38 MAPK activation and displays antitumor activity in vivo.PLoS One201276e3869810.1371/journal.pone.0038698 22701695
     [Google Scholar]
  179. AggarwalB.B. BhardwajA. AggarwalR.S. SeeramN.P. ShishodiaS. TakadaY. Role of resveratrol in prevention and therapy of cancer: Preclinical and clinical studies.Anticancer Res.2004245A27832840 15517885
     [Google Scholar]
  180. NilesR.M. McFarlandM. WeimerM.B. RedkarA. FuY.M. MeadowsG.G. Resveratrol is a potent inducer of apoptosis in human melanoma cells.Cancer Lett.2003190215716310.1016/S0304‑3835(02)00676‑6 12565170
     [Google Scholar]
  181. AhmadN. AdhamiV.M. AfaqF. FeyesD.K. MukhtarH. Resveratrol causes WAF-1/p21-mediated G(1)-phase arrest of cell cycle and induction of apoptosis in human epidermoid carcinoma A431 cells.Clin. Cancer Res.20017514661473 11350919
     [Google Scholar]
  182. LarrosaM. Tomás-BarberánF.A. EspínJ.C. Grape polyphenol resveratrol and the related molecule 4-hydroxystilbene induce growth inhibition, apoptosis, S-phase arrest, and upregulation of cyclins A, E, and B1 in human SK-Mel-28 melanoma cells.J. Agric. Food Chem.200351164576458410.1021/jf030073c 14705880
     [Google Scholar]
  183. ChoiJ.Y. HongW.G. ChoJ.H. Podophyllotoxin acetate triggers anticancer effects against non-small cell lung cancer cells by promoting cell death via cell cycle arrest, ER stress and autophagy.Int. J. Oncol.20154741257126510.3892/ijo.2015.3123 26314270
     [Google Scholar]
  184. LarrosaM. Tomás-BarberánF.A. EspínJ.C. The grape and wine polyphenol piceatannol is a potent inducer of apoptosis in human SK-Mel-28 melanoma cells.Eur. J. Nutr.200443527528410.1007/s00394‑004‑0471‑5 15309446
     [Google Scholar]
  185. PanzaE. TersigniM. IorizziM. Lauroside B, a megastigmane glycoside from Laurus nobilis (bay laurel) leaves, induces apoptosis in human melanoma cell lines by inhibiting NF-κB activation.J. Nat. Prod.201174222823310.1021/np100688g 21188975
     [Google Scholar]
  186. LoizzoM.R. TundisR. MenichiniF. SaabA.M. StattiG.A. MenichiniF. Cytotoxic activity of essential oils from labiatae and lauraceae families against in vitro human tumor models.Anticancer Res.2007275A32933299 17970073
     [Google Scholar]
  187. BrohemC.A. SawadaT.C.H. MassaroR.R. Apoptosis induction by 4-nerolidylcatechol in melanoma cell lines.Toxicol. In Vitro200923111111910.1016/j.tiv.2008.11.004 19059332
     [Google Scholar]
  188. MayolaE. GallerneC. EspostiD.D. Withaferin A induces apoptosis in human melanoma cells through generation of reactive oxygen species and down-regulation of Bcl-2.Apoptosis201116101014102710.1007/s10495‑011‑0625‑x 21710254
     [Google Scholar]
  189. WangJ.J. ShiQ.H. ZhangW. SandersonB.J.S. Anti-skin cancer properties of phenolic-rich extract from the pericarp of mangosteen (Garcinia mangostana Linn.).Food Chem. Toxicol.20125093004301310.1016/j.fct.2012.06.003 22705325
     [Google Scholar]
  190. WangJ.J. SandersonB.J.S. ZhangW. Cytotoxic effect of xanthones from pericarp of the tropical fruit mangosteen (Garcinia mangostana Linn.) on human melanoma cells.Food Chem. Toxicol.20114992385239110.1016/j.fct.2011.06.051 21723363
     [Google Scholar]
  191. Khuda-BukhshA.R. BhattacharyyaS.S. PaulS. BoujedainiN. Polymeric nanoparticle encapsulation of a naturally occurring plant scopoletin and its effects on human melanoma cell A375.J. Chin. Integr. Med.20108985386210.3736/jcim20100909 20836976
     [Google Scholar]
  192. LooiC.Y. MoharramB. PaydarM. Induction of apoptosis in melanoma A375 cells by a chloroform fraction of Centratherum anthelminticum (L.) seeds involves NF-kappaB, p53 and Bcl-2-controlled mitochondrial signaling pathways.BMC Complement. Altern. Med.201313116610.1186/1472‑6882‑13‑166 23837445
     [Google Scholar]
  193. AndroutsopoulosV.P. LiN. ArrooR.R.J. The methoxylated flavones eupatorin and cirsiliol induce CYP1 enzyme expression in MCF7 cells.J. Nat. Prod.20097281390139410.1021/np900051s 19601638
     [Google Scholar]
  194. KawaiiS TomonoY KataseE OgawaK YanoM Effect of citrus flavonoids on HL-60 cell differentiationAnticancer Res1999192 A12619
     [Google Scholar]
  195. KoW.C. LiuP.Y. ChenJ.L. LeuI.J. ShihC.M. Relaxant effects of flavonoids in isolated guinea pig trachea and their structure-activity relationships.Planta Med.200369121086109010.1055/s‑2003‑45187 14750022
     [Google Scholar]
  196. KatiyarS.K. AhmadN. MukhtarH. Green tea and skin.Arch. Dermatol.2000136898999410.1001/archderm.136.8.989 10926734
     [Google Scholar]
  197. RossJ.A. KasumC.M. Dietary flavonoids: Bioavailability, metabolic effects, and safety.Annu. Rev. Nutr.2002221193410.1146/annurev.nutr.22.111401.144957 12055336
     [Google Scholar]
  198. WeiH. TyeL. BresnickE. BirtD.F. Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice.Cancer Res.1990503499502 2105157
     [Google Scholar]
  199. BirtD.F. MitchellD. GoldB. PourP. PinchH.C. Inhibition of ultraviolet light induced skin carcinogenesis in SKH-1 mice by apigenin, a plant flavonoid.Anticancer Res.1997171A8591 9066634
     [Google Scholar]
  200. PatelD. ShuklaS. GuptaS. Apigenin and cancer chemoprevention: Progress, potential and promise. ReviewInt. J. Oncol.200730123324510.3892/ijo.30.1.233 17143534
     [Google Scholar]
  201. MirzoevaS. KimN.D. ChiuK. FranzenC.A. BerganR.C. PellingJ.C. Inhibition of HIF‐1 alpha and VEGF expression by the chemopreventive bioflavonoid apigenin is accompanied by Akt inhibition in human prostate carcinoma PC3‐M cells.Mol. Carcinog.200847968670010.1002/mc.20421 18240292
     [Google Scholar]
  202. FangJ. ZhouQ. LiuL.Z. Apigenin inhibits tumor angiogenesis through decreasing HIF-1 and VEGF expression.Carcinogenesis200628485886410.1093/carcin/bgl205 17071632
     [Google Scholar]
  203. McVeanM. XiaoH. IsobeK. PellingJ.C. Increase in wild-type p53 stability and transactivational activity by the chemopreventive agent apigenin in keratinocytes.Carcinogenesis200021463363910.1093/carcin/21.4.633 10753197
     [Google Scholar]
  204. TongX. PellingJ.C. Enhancement of p53 expression in keratinocytes by the bioflavonoid apigenin is associated with RNA‐binding protein HuR.Mol. Carcinog.200948211812910.1002/mc.20460 18680106
     [Google Scholar]
  205. WangW. HeidemanL. ChungC.S. PellingJ.C. KoehlerK.J. BirtD.F. Cell-cycle arrest at G2/M and growth inhibition by apigenin in human colon carcinoma cell lines.Mol. Carcinog.200028210211010.1002/1098‑2744(200006)28:2<102:AID‑MC6>3.0.CO;2‑2 10900467
     [Google Scholar]
  206. McVeanM. WeinbergW.C. PellingJ.C.A. p21 waf1 ‐independent pathway for inhibitory phosphorylation of cyclin‐dependent kinase p34 cdc2 and concomitant G 2/M arrest by the chemopreventive flavonoid apigenin.Mol. Carcinog.2002331364310.1002/mc.10016 11807956
     [Google Scholar]
  207. ZhuY. MaoY. ChenH. Apigenin promotes apoptosis, inhibits invasion and induces cell cycle arrest of T24 human bladder cancer cells.Cancer Cell Int.20131315410.1186/1475‑2867‑13‑54 23724790
     [Google Scholar]
  208. KimB.R. JeonY.K. NamM.J. A mechanism of apigenin-induced apoptosis is potentially related to anti-angiogenesis and anti-migration in human hepatocellular carcinoma cells.Food Chem. Toxicol.20114971626163210.1016/j.fct.2011.04.015 21515330
     [Google Scholar]
  209. GuptaS.C. KimJ.H. PrasadS. AggarwalB.B. Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals.Cancer Metastasis Rev.201029340543410.1007/s10555‑010‑9235‑2 20737283
     [Google Scholar]
  210. Van DrossR.T. HongX. EssengueS. FischerS.M. PellingJ.C. Modulation of UVB‐induced and basal cyclooxygenase‐2 (COX‐2) expression by apigenin in mouse keratinocytes: Role of USF transcription factors.Mol. Carcinog.200746430331410.1002/mc.20281 17186551
     [Google Scholar]
  211. TongX. Van DrossR.T. Abu-YousifA. MorrisonA.R. PellingJ.C. Apigenin prevents UVB-induced cyclooxygenase 2 expression: Coupled mRNA stabilization and translational inhibition.Mol. Cell. Biol.200727128329610.1128/MCB.01282‑06 17074806
     [Google Scholar]
  212. AraiY. WatanabeS. KimiraM. ShimoiK. MochizukiR. KinaeN. Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration.J. Nutr.200013092243225010.1093/jn/130.9.2243 10958819
     [Google Scholar]
  213. HaddadA.Q. VenkateswaranV. ViswanathanL. TeahanS.J. FleshnerN.E. KlotzL.H. Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines.Prostate Cancer Prostatic Dis.200691687610.1038/sj.pcan.4500845 16314891
     [Google Scholar]
  214. SuhY. AfaqF. KhanN. JohnsonJ.J. KhusroF.H. MukhtarH. Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cells.Carcinogenesis20103181424143310.1093/carcin/bgq115 20530556
     [Google Scholar]
  215. PalH.C. SharmaS. ElmetsC.A. AtharM. AfaqF. Fisetin inhibits growth, induces G2/M arrest and apoptosis of human epidermoid carcinoma A 431 cells: Role of mitochondrial membrane potential disruption and consequent caspases activation.Exp. Dermatol.201322747047510.1111/exd.12181 23800058
     [Google Scholar]
  216. ChenY.C. ShenS.C. LeeW.R. Wogonin and fisetin induction of apoptosis through activation of caspase 3 cascade and alternative expression of p21 protein in hepatocellular carcinoma cells SK-HEP-1.Arch. Toxicol.2002765-635135910.1007/s00204‑002‑0346‑6 12107653
     [Google Scholar]
  217. KhanN. AsimM. AfaqF. Abu ZaidM. MukhtarH. A novel dietary flavonoid fisetin inhibits androgen receptor signaling and tumor growth in athymic nude mice.Cancer Res.200868208555856310.1158/0008‑5472.CAN‑08‑0240 18922931
     [Google Scholar]
  218. MaherP. AkaishiT. AbeK. Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory.Proc. Natl. Acad. Sci. USA200610344165681657310.1073/pnas.0607822103 17050681
     [Google Scholar]
  219. HouD.X. FukudaM. JohnsonJ. MiyamoriK. UshikaiM. FujiiM. Fisetin induces transcription of NADPH:quinone oxidoreductase gene through an antioxidant responsive element-involved activation.Int. J. Oncol.20011861175117910.3892/ijo.18.6.1175 11351248
     [Google Scholar]
  220. SungB. PandeyM.K. AggarwalB.B. Fisetin, an inhibitor of cyclin-dependent kinase 6, down-regulates nuclear factor-kappaB-regulated cell proliferation, antiapoptotic and metastatic gene products through the suppression of TAK-1 and receptor-interacting protein-regulated IkappaBalpha kinase activation.Mol. Pharmacol.20077161703171410.1124/mol.107.034512 17387141
     [Google Scholar]
  221. YaoK. ZhangL. ZhangY. YeP. ZhuN. The flavonoid, fisetin, inhibits UV radiation-induced oxidative stress and the activation of NF-kappaB and MAPK signaling in human lens epithelial cells.Mol. Vis.20081418651871 18949064
     [Google Scholar]
  222. LéotoingL. WauquierF. GuicheuxJ. Miot-NoiraultE. WittrantY. CoxamV. The polyphenol fisetin protects bone by repressing NF-κB and MKP-1-dependent signaling pathways in osteoclasts.PLoS One201387e6838810.1371/journal.pone.0068388 23861901
     [Google Scholar]
  223. HeijnenC.G.M. HaenenG.R.M.M. VekemansJ.A.J.M. BastA. Peroxynitrite scavenging of flavonoids: Structure activity relationship.Environ. Toxicol. Pharmacol.200110419920610.1016/S1382‑6689(01)00083‑7
     [Google Scholar]
  224. ChangW.S. LeeY.J. LuF.J. ChiangH.C. Inhibitory effects of flavonoids on xanthine oxidase.Anticancer Res.1993136A21652170 8297130
     [Google Scholar]
  225. MutohM. TakahashiM. FukudaK. Suppression by flavonoids of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells: Structure-activity relationship.Jpn. J. Cancer Res.200091768669110.1111/j.1349‑7006.2000.tb01000.x 10920275
     [Google Scholar]
  226. TanakaT. MakitaH. KawabataK. Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin.Carcinogenesis199718595796510.1093/carcin/18.5.957 9163681
     [Google Scholar]
  227. TanakaT. MakitaH. OhnishiM. Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats by flavonoids diosmin and hesperidin, each alone and in combination.Cancer Res.1997572246252 9000563
     [Google Scholar]
  228. MakitaH. TanakaT. FujitsukaH. Chemoprevention of 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis by the dietary flavonoids chalcone, 2-hydroxychalcone, and quercetin.Cancer Res.1996562149044909 8895742
     [Google Scholar]
  229. KameiH. KoideT. KojimamT. Flavonoid-mediated tumor growth suppression demonstrated by in vivo study.Cancer Biother. Radiopharm.199611319319610.1089/cbr.1996.11.193 10851537
     [Google Scholar]
  230. CaltagironeS. RossiC. PoggiA. Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential.Int. J. Cancer200087459560010.1002/1097‑0215(20000815)87:4<595:AID‑IJC21>3.0.CO;2‑5 10918203
     [Google Scholar]
  231. HerndonJ.M. StuartP.M. FergusonT.A. Peripheral deletion of antigen-specific T cells leads to long-term tolerance mediated by CD8+ cytotoxic cells.J. Immunol.200517474098410410.4049/jimmunol.174.7.4098 15778368
     [Google Scholar]
  232. GasserS. OrsulicS. BrownE.J. RauletD.H. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor.Nature200543670541186119010.1038/nature03884 15995699
     [Google Scholar]
  233. KunduJ.K. ShinY.K. KimS.H. SurhY.J. Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-κB in mouse skin by blocking IκB kinase activity.Carcinogenesis20062771465147410.1093/carcin/bgi349 16474181
     [Google Scholar]
  234. NilesR.M. CookC.P. MeadowsG.G. FuY.M. McLaughlinJ.L. RankinG.O. Resveratrol is rapidly metabolized in athymic (nu/nu) mice and does not inhibit human melanoma xenograft tumor growth.J. Nutr.2006136102542254610.1093/jn/136.10.2542 16988123
     [Google Scholar]
  235. Reagan-ShawS. AfaqF. AzizM.H. AhmadN. Modulations of critical cell cycle regulatory events during chemoprevention of ultraviolet B-mediated responses by resveratrol in SKH-1 hairless mouse skin.Oncogene200423305151516010.1038/sj.onc.1207666 15122319
     [Google Scholar]
  236. OsmondG.W. AugustineC.K. ZipfelP.A. PadussisJ. TylerD.S. Enhancing melanoma treatment with resveratrol.J. Surg. Res.2012172110911510.1016/j.jss.2010.07.033 20855085
     [Google Scholar]
  237. TianX. GaoR. ZhangX. Insecticidal activity of deoxypodophyllotoxin.Acta Universitatis Agriculturalis Boreali-occidentalis2000281924
     [Google Scholar]
  238. AnantharajuP.G. GowdaP.C. VimalambikeM.G. MadhunapantulaS.V. An overview on the role of dietary phenolics for the treatment of cancers.Nutr. J.20161519910.1186/s12937‑016‑0217‑2 27903278
     [Google Scholar]
  239. KumarN. GoelN. Phenolic acids: Natural versatile molecules with promising therapeutic applications.Biotechnol. Rep. (Amst.)201924e0037010.1016/j.btre.2019.e00370 31516850
     [Google Scholar]
  240. PereiraD. ValentãoP. PereiraJ. AndradeP. Phenolics: From chemistry to biology.Molecules20091462202221110.3390/molecules14062202
     [Google Scholar]
  241. CliffordM.N. Chlorogenic acids and other cinnamates - nature, occurrence and dietary burden.J. Sci. Food Agric.199979336237210.1002/(SICI)1097‑0010(19990301)79:3<362:AID‑JSFA256>3.0.CO;2‑D
     [Google Scholar]
  242. RashmiH.B. NegiP.S. Phenolic acids from vegetables: A review on processing stability and health benefits.Food Res. Int.202013610929810.1016/j.foodres.2020.109298 32846511
     [Google Scholar]
  243. D’ArchivioM. FilesiC. Di BenedettoR. GargiuloR. GiovanniniC. MasellaR. Polyphenols, dietary sources and bioavailability.Ann. Ist. Super. Sanita2007434348361 18209268
     [Google Scholar]
  244. De MarinoS. BorboneN. ZolloF. IanaroA. Di MeglioP. IorizziM. Megastigmane and phenolic components from Laurus nobilis L. leaves and their inhibitory effects on nitric oxide production.J. Agric. Food Chem.200452257525753110.1021/jf048782t 15675799
     [Google Scholar]
  245. LiuL. PohlN.L.B. Synthesis of a series of maltotriose phosphates with an evaluation of the utility of a fluorous phosphate protecting group.Carbohydr. Res.2013369142410.1016/j.carres.2012.12.015 23376679
     [Google Scholar]
  246. DingN. Synthesis and antibacterial evaluation of a series of acetylated oligorhamnoside derivatives.Carbohydr. Res.20113462126213510.1016/j.carres.2011.07.028 21864832
     [Google Scholar]
  247. DingN. ZhangW. LvG. LiY. Synthesis and biological evaluation of antifungal activities of novel 1,2-trans glycosphingolipids.Arch. Pharm. (Weinheim)20113441278679310.1002/ardp.201000335 21987208
     [Google Scholar]
  248. TaoY. DingN. RenS. LiY. Heck-type cross-coupling between halo-exo-glycals and endo-glycals: A practical way to achieve C-glycosidic disaccharides.Tetrahedron Lett.201354456101610410.1016/j.tetlet.2013.08.118
     [Google Scholar]
  249. IlcT. ParageC. BoachonB. NavrotN. Werck-ReichhartD. Monoterpenol oxidative metabolism: Role in plant adaptation and potential applications.Front Plant Sci2016750910.3389/fpls.2016.00509 27200002
     [Google Scholar]
  250. ApiA.M. BelsitoD. BhatiaS. RIFM fragrance ingredient safety assessment, Linalool, CAS registry number 78-70-6.Food Chem. Toxicol.201582Suppl.S29S38
     [Google Scholar]
  251. ChengY. DaiC. ZhangJ. SIRT3-SOD2-ROS pathway is involved in Linalool-induced glioma cell apoptotic death.Acta Biochim. Pol.201764234335010.18388/abp.2016_1438 28567457
     [Google Scholar]
  252. JanaS. PatraK. SarkarS. Antitumorigenic potential of linalool is accompanied by modulation of oxidative stress: An in vivo study in sarcoma-180 solid tumor model.Nutr. Cancer201466583584810.1080/01635581.2014.904906 24779766
     [Google Scholar]
  253. RopkeC.D. da SilvaV.V. KeraC.Z. In vitro and in vivo inhibition of skin matrix metalloproteinases by Pothomorphe umbellata root extract.Photochem. Photobiol.200682243944210.1562/2005‑06‑29‑RA‑596 16613496
     [Google Scholar]
  254. BrohemC.A. MassaroR.R. TiagoM. Proteasome inhibition and ROS generation by 4‐nerolidylcatechol induces melanoma cell death.Pigment Cell Melanoma Res.201225335436910.1111/j.1755‑148X.2012.00992.x 22372875
     [Google Scholar]
  255. BushJ.A. CheungK.J.J.Jr LiG. Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53.Exp. Cell Res.2001271230531410.1006/excr.2001.5381 11716543
     [Google Scholar]
  256. DeviP.U. SharadaA.C. SolomonF.E. In vivo growth inhibitory and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma.Cancer Lett.1995951-218919310.1016/0304‑3835(95)03892‑Z 7656229
     [Google Scholar]
  257. DeviP.U. KamathR. Radiosensitizing effect of withaferin A combined with hyperthermia on mouse fibrosarcoma and melanoma.J. Radiat. Res. (Tokyo)20034411610.1269/jrr.44.1 12841592
     [Google Scholar]
  258. DeviP.U. KamathR. RaoB.S. Radiosensitization of a mouse melanoma by withaferin A: In vivo studies.Indian J. Exp. Biol.2000385432437 11272405
     [Google Scholar]
  259. SamadiA.K. CohenS.M. MukerjiR. Natural withanolide withaferin A induces apoptosis in uveal melanoma cells by suppression of Akt and c-MET activation.Tumour Biol.20123341179118910.1007/s13277‑012‑0363‑x 22477711
     [Google Scholar]
  260. LiW. ZhangC. DuH. Withaferin A suppresses the up-regulation of acetyl-coA carboxylase 1 and skin tumor formation in a skin carcinogenesis mouse model.Mol. Carcinog.2016Nov55111739174610.1002/mc.22423
     [Google Scholar]
  261. Varache-LembègeM. MoreauS. LarroutureS. MontaudonD. RobertJ. NuhrichA. Synthesis and antiproliferative activity of aryl- and heteroaryl-hydrazones derived from xanthone carbaldehydes.Eur. J. Med. Chem.20084361336134310.1016/j.ejmech.2007.09.003 17949859
     [Google Scholar]
  262. LuoL. QinJ.K. DaiZ.K. GaoS.H. Synthesis and biological evaluation of novel benzo[b]xanthone derivatives as potential antitumor agents.J. Serb. Chem. Soc.20137891301130810.2298/JSC120925060L
     [Google Scholar]
  263. LiC.L. HanX.C. ZhangH. WuJ.S. LiB. Effect of scopoletin on apoptosis and cell cycle arrest in human prostate cancer cells in vitro.Trop. J. Pharm. Res.201514461161710.4314/tjpr.v14i4.8
     [Google Scholar]
  264. AsgarM.A. SenawongG. SripaB. SenawongT. Scopoletin potentiates the anticancer effects of cisplatin against cholangiocarcinoma cell lines.Bangladesh J. Pharmacol.2015101697710.3329/bjp.v10i1.21202
     [Google Scholar]
  265. YuN. LiN. WangK. Design, synthesis and biological activity evaluation of novel scopoletin-NO donor derivatives against MCF-7 human breast cancer in vitro and in vivo.Eur. J. Med. Chem.202122411370110.1016/j.ejmech.2021.113701 34315044
     [Google Scholar]
  266. BanikazemiZ. MirazimiS.M. DashtiF. Coumarins, and gastrointestinal cancer: A new therapeutic option?Front. Oncol.20211175278410.3389/fonc.2021.752784 34707995
     [Google Scholar]
  267. KupchanS.M. HemingwayR.J. KarimA. WernerD. Tumor inhibitors. XLVII. Vernodalin and vernomygdin, two new cytotoxic sesquiterpene lactones from Vernonia amygdalina del.J. Org. Chem.196934123908391110.1021/jo01264a035 5357533
     [Google Scholar]
  268. LooiC.Y. AryaA. CheahF.K. Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum(L.) seeds.PLoS One201382e5664310.1371/journal.pone.0056643 23437193
     [Google Scholar]
  269. JonasW.B. Advising patients on the use of complementary and alternative medicine.Appl Psychophysiol Bio200126320521410.1023/A:1011398120476 11680284
     [Google Scholar]
  270. LiuY. NugrohoA.E. HirasawaY. Vernodalidimers A and B, novel orthoester elemanolide dimers from seeds of Vernonia anthelmintica.Tetrahedron Lett.201051506584658710.1016/j.tetlet.2010.10.031
     [Google Scholar]
  271. JoosS. GlassenK. MusselmannB. Herbal medicine in primary healthcare in Germany: The patient’s perspective.Evid. Based Complement. Alternat. Med.2012201211010.1155/2012/294638 23346197
     [Google Scholar]
/content/journals/cctr/10.2174/0115733947302449240522063702
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Plant-derived Molecules as Potent Anti-skin Cancer Agents
Curr Cancer Ther Rev 21, 487 (2025); https://doi.org/10.2174/0115733947302449240522063702
/content/journals/cctr/10.2174/0115733947302449240522063702
/content/journals/cctr/10.2174/0115733947302449240522063702
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  • Article Type:     Review Article
Keyword(s): anti-cancer; crude plant extracts; melanoma; phytochemical; Skin cancer; structural activity relationship

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