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Abstract

Natural coumarins, a class of compounds found abundantly in various plants, are emerging as promising candidates in fight against cancer. Their ability to target multiple cancer-related processes has drawn significant interest from researchers. Natural coumarins exhibit anticancer effects through mechanisms such as inducing apoptosis, which is the programmed death of cancer cells, inhibiting cell proliferation, and disrupting angiogenesis, the process by which tumors develop their own blood supply to sustain growth. What makes coumarins particularly intriguing is their broad-spectrum activity against various types of cancer cells, from breast to lung to colon cancers. They interact with key molecular pathways that drive tumor progression, making them versatile agents in cancer therapy. Additionally, unlike many conventional chemotherapy drugs, natural coumarins generally have lower toxicity, which could translate to fewer side effects for patients. This characteristic makes them attractive as potential standalone treatments or as complementary therapies that enhance the efficacy of existing drugs while minimizing harm to normal cells. Ongoing research continues to explore the therapeutic potential of natural coumarins to better understand their full therapeutic potential and how they might work in combination with other anticancer agents. As the body of evidence grows, these natural compounds could become integral components of more effective and less harmful cancer treatment regimens, offering new hope for patients facing this challenging disease. This review was conducted by systematically analyzing the existing literature on natural coumarins and their anticancer potential.

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2025-06-19
2025-09-04

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References

  1. Siegel R.L. Miller K.D. Wagle N.S. Jemal A. Cancer statistics, 2023. CA Cancer J. Clin. 2023 73 1 17 48 10.3322/caac.21763 36633525
    [Google Scholar]
  2. Bray F. Laversanne M. Sung H. Ferlay J. Siegel R.L. Soerjomataram I. Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2024 74 3 229 263 10.3322/caac.21834 38572751
    [Google Scholar]
  3. Song Q. Merajver S.D. Li J.Z. Cancer classification in the genomic era: Five contemporary problems. Hum. Genomics 2015 9 1 27 10.1186/s40246‑015‑0049‑8 26481255
    [Google Scholar]
  4. Hassanpour S.H. Dehghani M. Review of cancer from perspective of molecular. J. Cancer Res. Practice 2017 4 4 127 129 10.1016/j.jcrpr.2017.07.001
    [Google Scholar]
  5. Ranjan A. Ramachandran S. Gupta N. Kaushik I. Wright S. Srivastava S. Das H. Srivastava S. Prasad S. Srivastava S.K. Role of phytochemicals in cancer prevention. Int. J. Mol. Sci. 2019 20 20 4981 10.3390/ijms20204981 31600949
    [Google Scholar]
  6. Aydın T. Gümüştaş M. Sancı T.Ö. Çakır A. Herniarin and skimmin coumarins in spice and edible plants and their benefits for health. In:Studies in Natural Products Chemistry 2024 339 365 10.1016/B978‑0‑443‑15628‑1.00010‑6
    [Google Scholar]
  7. Zhang L. Xu Z. Coumarin-containing hybrids and their anticancer activities. Eur. J. Med. Chem. 2019 181 111587 10.1016/j.ejmech.2019.111587 31404864
    [Google Scholar]
  8. Matos M.J. Santana L. Uriarte E. Abreu O.A. Molina E. Yordi E.G. Coumarins — An important class of phytochemicals In:Phytochemicals - Isolation, Characterisation and Role in Human Health 2015 InTech 10.5772/59982
    [Google Scholar]
  9. Küpeli Akkol E. Genç Y. Karpuz B. Sobarzo-Sánchez E. Capasso R. Coumarins and coumarin-related compounds in pharmacotherapy of cancer. Cancers 2020 12 7 1959 10.3390/cancers12071959 32707666
    [Google Scholar]
  10. Khursheed A. Jain V. Medicinal research progress of natural coumarin and its derivatives. Nat. Prod. J. 2021 11 5 648 662 10.2174/22103163MTExpMTAk5
    [Google Scholar]
  11. Yadav A.K. Maharjan Shrestha R. Yadav P.N. Anticancer mechanism of coumarin-based derivatives. Eur. J. Med. Chem. 2024 267 116179 10.1016/j.ejmech.2024.116179 38340509
    [Google Scholar]
  12. Önder A. Anticancer activity of natural coumarins for biological targets. Studies in Natural Products Chemistry Elsevier 2020 64 85 109 10.1016/B978‑0‑12‑817903‑1.00003‑6
    [Google Scholar]
  13. Venugopala K.N. Rashmi V. Odhav B. Review on natural coumarin lead compounds for their pharmacological activity. BioMed Res. Int. 2013 2013 1 14 10.1155/2013/963248 23586066
    [Google Scholar]
  14. Kostova I. Synthetic and natural coumarins as cytotoxic agents. Curr. Med. Chem. Anticancer Agents 2005 5 1 29 46 10.2174/1568011053352550 15720259
    [Google Scholar]
  15. Hussain M.I. Syed Q.A. Khattak M.N.K. Hafez B. Reigosa M.J. El-Keblawy A. Natural product coumarins: Biological and pharmacological perspectives. Biologia 2019 74 7 863 888 10.2478/s11756‑019‑00242‑x
    [Google Scholar]
  16. Kaur M. Kohli S. Sandhu S. Bansal Y. Bansal G. Coumarin: A promising scaffold for anticancer agents. Anticancer. Agents Med. Chem. 2015 15 8 1032 1048 10.2174/1871520615666150101125503 25553437
    [Google Scholar]
  17. Rubab L. Afroz S. Ahmad S. Hussain S. Nawaz I. Irfan A. Batool F. Kotwica-Mojzych K. Mojzych M. An update on synthesis of coumarin sulfonamides as enzyme inhibitors and anticancer agents. Molecules 2022 27 5 1604 10.3390/molecules27051604 35268704
    [Google Scholar]
  18. Stefanachi A. Leonetti F. Pisani L. Catto M. Carotti A. Coumarin: A natural, privileged and versatile scaffold for bioactive compounds. Molecules 2018 23 2 250 10.3390/molecules23020250 29382051
    [Google Scholar]
  19. Menezes J.C.J.M.D.S. Diederich M. Translational role of natural coumarins and their derivatives as anticancer agents. Future Med. Chem. 2019 11 9 1057 1082 10.4155/fmc‑2018‑0375 31140865
    [Google Scholar]
  20. Katari N.K. Bala M.D. Shaik B.B. Seboletswe P. Gundla R. Kushwaha N.D. Kumar V. Singh P. Karpoormath R. Recent literature review on coumarin hybrids as potential anticancer agents. Anticancer. Agents Med. Chem. 2023 23 2 142 163 10.2174/1871520622666220418143438 35440315
    [Google Scholar]
  21. Melfi F. Carradori S. Angeli A. D’Agostino I. Nature as a source and inspiration for human monoamine oxidase B (hMAO-B) inhibition: A review of the recent advances in chemical modification of natural compounds. Expert Opin. Drug Discov. 2023 18 8 851 879 10.1080/17460441.2023.2226860 37332199
    [Google Scholar]
  22. Sharifi-Rad J. Cruz-Martins N. López-Jornet P. Lopez E.P.F. Harun N. Yeskaliyeva B. Beyatli A. Sytar O. Shaheen S. Sharopov F. Taheri Y. Docea A.O. Calina D. Cho W.C. Natural coumarins: Exploring the pharmacological complexity and underlying molecular mechanisms. Oxid. Med. Cell. Longev. 2021 2021 1 6492346 10.1155/2021/6492346 34531939
    [Google Scholar]
  23. Zhu J.J. Jiang J.G. Pharmacological and nutritional effects of natural coumarins and their structure–activity relationships. Mol. Nutr. Food Res. 2018 62 14 1701073 10.1002/mnfr.201701073 29750855
    [Google Scholar]
  24. Venketeshwer Rao L.R. Phytochemicals - Isolation, Characterisation and Role in Human Health. InTech 2015 10.5772/58648
    [Google Scholar]
  25. Jain P.K. Joshi H. Coumarin: Chemical and pharmacological profile. J. Appl. Pharm. Sci. 2012 2 236 240 10.7324/JAPS.2012.2643
    [Google Scholar]
  26. Garg S.S. Gupta J. Sharma S. Sahu D. An insight into the therapeutic applications of coumarin compounds and their mechanisms of action. Eur. J. Pharm. Sci. 2020 152 105424 10.1016/j.ejps.2020.105424 32534193
    [Google Scholar]
  27. Hoult J.R.S. Payá M. Pharmacological and biochemical actions of simple coumarins: Natural products with therapeutic potential. Gen. Pharmacol. 1996 27 4 713 722 10.1016/0306‑3623(95)02112‑4 8853310
    [Google Scholar]
  28. Melough M.M. Cho E. Chun O.K. Furocoumarins: A review of biochemical activities, dietary sources and intake, and potential health risks. Food Chem. Toxicol. 2018 113 99 107 10.1016/j.fct.2018.01.030 29378230
    [Google Scholar]
  29. Traven V.F. New synthetic routes to furocoumarins and their analogs: A review. Molecules 2004 9 3 50 66 10.3390/90300050 18007411
    [Google Scholar]
  30. Ustalar A. Yilmaz M. Osmani̇ A. Keçeli̇ S.A. Synthesis and antifungal activity of new dihydrofurocoumarins and dihydrofuroquinolines. Turk. J. Chem. 2017 41 80 88 10.3906/kim‑1604‑22
    [Google Scholar]
  31. Kim Y.A. Lee J.I. Kong C.S. Choe J.C. Oh K. Seo Y. Antioxidant activity of dihydrofurocoumarins from Corydalis heterocarpa. Biotechnol. Bioprocess Eng.; BBE 2014 19 5 771 779 10.1007/s12257‑014‑0462‑1
    [Google Scholar]
  32. Egger M.D. Liu Y. Sevčík J. Tesařová E. Rozhkov R. Larock R.C. Armstrong D.W. Enantioseparation of dihydrofurocoumarin derivatives by various separation modes of capillary electrophoresis. Electrophoresis 2003 24 15 2650 2656 10.1002/elps.200305511 12900878
    [Google Scholar]
  33. Khandy M.T. Sofronova A.K. Gorpenchenko T.Y. Chirikova N.K. Plant pyranocoumarins: Description, biosynthesis, application. Plants 2022 11 22 3135 10.3390/plants11223135 36432864
    [Google Scholar]
  34. Mukherjee A. Mahato S. Zyryanov G.V. Majee A. Santra S. Diverse synthesis of pyrano[3,2-c]coumarins: A brief update. New J. Chem. 2020 44 44 18980 18993 10.1039/D0NJ03846F
    [Google Scholar]
  35. Siddiqui Z.N. Sulfamic acid catalysed synthesis of pyranocoumarins in aqueous media. Tetrahedron Lett. 2014 55 1 163 168 10.1016/j.tetlet.2013.10.142
    [Google Scholar]
  36. Kirsch G. Abdelwahab A. Chaimbault P. Natural and synthetic coumarins with effects on inflammation. Molecules 2016 21 10 1322 10.3390/molecules21101322 27706093
    [Google Scholar]
  37. Desta K.T. Abd El-Aty A.M. Millettia isoflavonoids: A comprehensive review of structural diversity, extraction, isolation, and pharmacological properties. Phytochem. Rev. 2023 22 1 275 308 10.1007/s11101‑022‑09845‑w 36345415
    [Google Scholar]
  38. Matos M.J. Uriarte E. Santana L. 3-Phenylcoumarins as a privileged scaffold in medicinal chemistry: The landmarks of the past decade. Molecules 2021 26 21 6755 10.3390/molecules26216755 34771164
    [Google Scholar]
  39. Sashidhara K.V. Rao K.B. Singh S. Modukuri R.K. Aruna Teja G. Chandasana H. Shukla S. Bhatta R.S. Synthesis and evaluation of new 3-phenylcoumarin derivatives as potential antidepressant agents. Bioorg. Med. Chem. Lett. 2014 24 20 4876 4880 10.1016/j.bmcl.2014.08.037 25239852
    [Google Scholar]
  40. Mustafa Y. Mohammed E. Khalil R. Synthesis, characterization, and anticoagulant activity of new functionalized biscoumarins. Egypt. J. Chem. 2021 64 8 4461 4468 10.21608/ejchem.2021.73699.3641
    [Google Scholar]
  41. Salar U. Nizamani A. Arshad F. Khan K.M. Fakhri M.I. Perveen S. Ahmed N. Choudhary M.I. Bis-coumarins; non-cytotoxic selective urease inhibitors and antiglycation agents. Bioorg. Chem. 2019 91 103170 10.1016/j.bioorg.2019.103170 31408830
    [Google Scholar]
  42. Ren Q.C. Gao C. Xu Z. Feng L.S. Liu M.L. Wu X. Zhao F. Bis-coumarin derivatives and their biological activities. Curr. Top. Med. Chem. 2018 18 2 101 113 10.2174/1568026618666180221114515 29473509
    [Google Scholar]
  43. Song X.F. Fan J. Liu L. Liu X.F. Gao F. Coumarin derivatives with anticancer activities: An update. Arch. Pharm. 2020 353 8 2000025 10.1002/ardp.202000025 32383190
    [Google Scholar]
  44. Al-Warhi T. Sabt A. Elkaeed E.B. Eldehna W.M. Recent advancements of coumarin-based anticancer agents: An up-to-date review. Bioorg. Chem. 2020 103 104163 10.1016/j.bioorg.2020.104163 32890989
    [Google Scholar]
  45. Önder A. Anticancer activity of natural coumarins for biological targets. Studies in Natural Products Chemistry. Elsevier 2020 85 109 10.1016/B978‑0‑12‑817903‑1.00003‑6
    [Google Scholar]
  46. Gangopadhyay A. Plant-derived natural coumarins with anticancer potentials: Future and challenges. J. Herb. Med. 2023 42 100797 10.1016/j.hermed.2023.100797
    [Google Scholar]
  47. Riviere C. Goossens L. Pommery N. Fourneau C. Delelis A. Henichart J.P. Antiproliferative effects of isopentenylated coumarins isolated from Phellolophium madagascariense Baker. Nat. Prod. Res. 2006 20 10 909 916 10.1080/14786410500277787 16854718
    [Google Scholar]
  48. Jeon Y.J. Jang J.Y. Shim J.H. Myung P.K. Chae J.I. Esculetin, a coumarin derivative, exhibits anti-proliferative and pro-apoptotic activity in G361 human malignant melanoma. J. Cancer Prev. 2015 20 2 106 112 10.15430/JCP.2015.20.2.106 26151043
    [Google Scholar]
  49. Bai Y. Li D. Zhou T. Qin N. Li Z. Yu Z. Hua H. Coumarins from the roots of Angelica dahurica with antioxidant and antiproliferative activities. J. Funct. Foods 2016 20 453 462 10.1016/j.jff.2015.11.018
    [Google Scholar]
  50. Vázquez R. Riveiro M.E. Vermeulen M. Mondillo C. Coombes P.H. Crouch N.R. Ismail F. Mulholland D.A. Baldi A. Shayo C. Davio C. Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells. Phytomedicine 2012 19 8-9 737 746 10.1016/j.phymed.2012.03.008 22537907
    [Google Scholar]
  51. Zhang L. Jiang G. Yao F. He Y. Liang G. Zhang Y. Hu B. Wu Y. Li Y. Liu H. Growth inhibition and apoptosis induced by osthole, a natural coumarin, in hepatocellular carcinoma. PLoS One 2012 7 5 e37865 10.1371/journal.pone.0037865 22662241
    [Google Scholar]
  52. Tosun F. Biltekin S.N. Karadağ A.E. Mıhoğlugil F. Akalgan D. Miski M. Biological activities of the natural coumarins from apiaceae plants. Rec. Nat. Prod. 2023 17 867 877 10.6135/rnp.396.2304.2758
    [Google Scholar]
  53. Jiménez-Orozco F.A. Randeloviç I. Hegedüs Z. Vega-Lopez A. Martínez-Flores F. Tóvarí J. In vitro anti-proliferative effect and in vivo antitumor action of daphnetin in different tumor cells. Cir. Cir. 2020 88 6 765 771 10.24875/CIRU.20000197 33254179
    [Google Scholar]
  54. Chahardoli A. Mavaei M. Shokoohinia Y. Fattahi A. Galbanic acid, a sesquiterpene coumarin as a novel candidate for the biosynthesis of silver nanoparticles: In vitro hemocompatibility, antiproliferative, antibacterial, antioxidant, and anti-inflammatory properties. Adv. Powder Technol. 2023 34 1 103928 10.1016/j.apt.2022.103928
    [Google Scholar]
  55. Wróblewska-Łuczka P. Grabarska A. Florek-Łuszczki M. Plewa Z. Łuszczki J.J. Synergy, additivity, and antagonism between cisplatin and selected coumarins in human melanoma cells. Int. J. Mol. Sci. 2021 22 2 537 10.3390/ijms22020537 33430369
    [Google Scholar]
  56. Shokoohinia Y. Hosseinzadeh L. Alipour M. Mostafaie A. Mohammadi-Motlagh H.R. Comparative evaluation of cytotoxic and apoptogenic effects of several coumarins on human cancer cell lines: Osthole induces apoptosis in p53-deficient H1299 cells. Adv. Pharmacol. Sci. 2014 2014 1 8 10.1155/2014/847574 25276123
    [Google Scholar]
  57. Francisco C.S. Rodrigues L.R. Cerqueira N.M.F.S.A. Oliveira-Campos A.M.F. Rodrigues L.M. Synthesis of novel benzofurocoumarin analogues and their anti-proliferative effect on human cancer cell lines. Eur. J. Med. Chem. 2012 47 1 370 376 10.1016/j.ejmech.2011.11.005 22119152
    [Google Scholar]
  58. Mah S.H. Teh S.S. Ismail A.A.F. Ee G.C.L. Anti-proliferative effects of a coumarin benjaminin on four human cancer cell lines. PSR 2020 7 1 7 10.7454/psr.v7i1.1057
    [Google Scholar]
  59. Singh R. Exploring the interplay between apoptosis and coumarins: A comprehensive analysis. Bio Science Research Bulletin 2023 39 2 75 77 10.48165/bpas.2023.39.2.5
    [Google Scholar]
  60. Savitskaya M.A. Onishchenko G.E. Mechanisms of apoptosis. Biochemistry 2015 80 11 1393 1405 10.1134/S0006297915110012 26615431
    [Google Scholar]
  61. Wu Y. Xu J. Liu Y. Zeng Y. Wu G. A review on anti-tumor mechanisms of coumarins. Front. Oncol. 2020 10 592853 10.3389/fonc.2020.592853 33344242
    [Google Scholar]
  62. Zhang L. Tong X. Zhang J. Huang J. Wang J. DAW22, a natural sesquiterpene coumarin isolated from Ferula ferulaeoides (Steud.) Korov. that induces C6 glioma cell apoptosis and endoplasmic reticulum (ER) stress. Fitoterapia 2015 103 46 54 10.1016/j.fitote.2015.03.010 25776007
    [Google Scholar]
  63. Wang J.L. Sang C.Y. Wang J. Li P.L. Chai T. Naghavi M.R. Zhao Y.M. Yang J.L. Sesquiterpene coumarins from Ferula sinkiangensis and their anti-pancreatic cancer effects. Phytochemistry 2023 214 113824 10.1016/j.phytochem.2023.113824 37597719
    [Google Scholar]
  64. Vianna D.R. Hamerski L. Figueiró F. Bernardi A. Visentin L.C. Pires E.N.S. Teixeira H.F. Salbego C.G. Eifler-Lima V.L. Battastini A.M.O. von Poser G.L. Pinto A.C. Selective cytotoxicity and apoptosis induction in glioma cell lines by 5-oxygenated-6,7-methylenedioxycoumarins from Pterocaulon species. Eur. J. Med. Chem. 2012 57 268 274 10.1016/j.ejmech.2012.09.007 23069682
    [Google Scholar]
  65. Kim A.D. Han X. Piao M.J. Hewage S.R.K.M. Hyun C.L. Cho S.J. Hyun J.W. Esculetin induces death of human colon cancer cells via the reactive oxygen species-mediated mitochondrial apoptosis pathway. Environ. Toxicol. Pharmacol. 2015 39 2 982 989 10.1016/j.etap.2015.03.003 25818986
    [Google Scholar]
  66. Lou L.L. Zhao P. Cheng Z.Y. Guo R. Yao G.D. Wang X.B. Huang X.X. Song S.J. A new coumarin from Juglans mandshurica Maxim induce apoptosis in hepatocarcinoma cells. Nat. Prod. Res. 2019 33 12 1791 1793 10.1080/14786419.2018.1434646 29397774
    [Google Scholar]
  67. Hasanzadeh D. Mahdavi M. Dehghan G. Charoudeh H.N. Farnesiferol C induces cell cycle arrest and apoptosis mediated by oxidative stress in MCF-7 cell line. Toxicol. Rep. 2017 4 420 426 10.1016/j.toxrep.2017.07.010 28959668
    [Google Scholar]
  68. Zhang C-G. Huang J-C. Liu T. Li X-Y. Anticancer effects of bishydroxycoumarin are mediated through apoptosis induction, cell migration inhibition and cell cycle arrest in human glioma cells. J. BUON 2015 20 6 1592 1600 [PMID: 26854457
    [Google Scholar]
  69. Gong J. Zhang W-G. Feng X-F. Shao M-J. Xing C. Aesculetin (6,7-dihydroxycoumarin) exhibits potent and selective antitumor activity in human acute myeloid leukemia cells (THP-1) via induction of mitochondrial mediated apoptosis and cancer cell migration inhibition. J. BUON 2017 22 6 1563 1569 [PMID: 29332353
    [Google Scholar]
  70. Park S.B. Jung W. Kim H. Yu H.Y. Kim Y. Kim J. Esculetin has therapeutic potential via the proapoptotic signaling pathway in A253 human submandibular salivary gland tumor cells. Exp. Ther. Med. 2022 24 2 533 10.3892/etm.2022.11460 35837055
    [Google Scholar]
  71. Li J. Fu Y. Hu X. Xiong Y. Psoralidin inhibits the proliferation of human liver cancer cells by triggering cell cycle arrest, apoptosis and autophagy and inhibits tumor growth in vivo. J. BUON 2019 24 5 1950 1955 [PMID: 31786860
    [Google Scholar]
  72. Zhang Y. Wang L. Deng Y. Zhao P. Deng W. Zhang J. Luo J. Li R. Fraxetin suppresses proliferation of non-small-cell lung cancer cells via preventing activation of signal transducer and activator of transcription 3. Tohoku J. Exp. Med. 2019 248 1 3 12 10.1620/tjem.248.3 31080186
    [Google Scholar]
  73. Arbab I.A. Looi C.Y. Abdul A.B. Cheah F.K. Wong W.F. Sukari M.A. Abdullah R. Mohan S. Syam S. Arya A. Mohamed Elhassan Taha M. Muharram B. Rais Mustafa M. Ibrahim Abdelwahab S. Dentatin induces apoptosis in prostate cancer cells via Bcl-2, Bcl-xL, survivin downregulation, Caspase-9, -3/7 activation, and NF- κ B inhibition. Evid. Based Complement. Alternat. Med. 2012 2012 1 15 10.1155/2012/856029 23091559
    [Google Scholar]
  74. Li C.L. Han X.C. Zhang H. Wu J.S. Li B. Effect of scopoletin on apoptosis and cell cycle arrest in human prostate cancer cells in vitro. Trop. J. Pharm. Res. 2015 14 4 611 10.4314/tjpr.v14i4.8
    [Google Scholar]
  75. Wang Q. Wang Y-P. Lin H. Zhang L-Q. Wu L-J. Pang L-X. Antiproliferative and apoptotic effects of angelicin in highly invasive prostate cancer cells. Trop. J. Pharm. Res. 2015 14 8 1405 10.4314/tjpr.v14i8.12
    [Google Scholar]
  76. Shahzadi I. Ali Z. Baek S.H. Mirza B. Ahn K.S. Assessment of the antitumor potential of umbelliprenin, a naturally occurring sesquiterpene coumarin. Biomedicines 2020 8 5 126 10.3390/biomedicines8050126 32443431
    [Google Scholar]
  77. Kang J.I. Hong J.Y. Choi J.S. Lee S.K. Columbianadin inhibits cell proliferation by inducing apoptosis and necroptosis in HCT116 colon cancer cells. Biomol. Ther. (Seoul) 2016 24 3 320 327 10.4062/biomolther.2015.145 27098859
    [Google Scholar]
  78. Suparji N.S. Chan G. Sapili H. Arshad N.M. In, L.L.A.; Awang, K.; Hasima Nagoor, N. Geranylated 4-phenylcoumarins exhibit anticancer effects against human prostate cancer cells through caspase-independent mechanism. PLoS One 2016 11 3 e0151472 10.1371/journal.pone.0151472 26974436
    [Google Scholar]
  79. Mazimba O. Umbelliferone: Sources, chemistry and bioactivities review. Bull. Fac. Pharm. Cairo Univ. 2017 55 2 223 232 10.1016/j.bfopcu.2017.05.001
    [Google Scholar]
  80. Yu S.M. Hu D.H. Zhang J.J. Umbelliferone exhibits anticancer activity via the induction of apoptosis and cell cycle arrest in HepG2 hepatocellular carcinoma cells. Mol. Med. Rep. 2015 12 3 3869 3873 10.3892/mmr.2015.3797 25997538
    [Google Scholar]
  81. Anbaji F.Z. Zargar S.J. Tavakoli S. Effect of isolated grandivittin from Ferulago trifida Boiss. (Apiaceae) on the proliferation and apoptosis of human lung cancer A549 cells. Naunyn Schmiedebergs Arch. Pharmacol. 2023 396 7 1525 1533 10.1007/s00210‑023‑02419‑3 36786818
    [Google Scholar]
  82. Velasco-Velázquez M.A. Salinas-Jazmín N. Mendoza-Patiño N. Mandoki J.J. Reduced paxillin expression contributes to the antimetastatic effect of 4-hydroxycoumarin on B16-F10 melanoma cells. Cancer Cell Int. 2008 8 1 8 10.1186/1475‑2867‑8‑8 18492274
    [Google Scholar]
  83. Salinas-Jazmín N. de la Fuente M. Jaimez R. Pérez-Tapia M. Pérez-Torres A. Velasco-Velázquez M.A. Antimetastatic, antineoplastic, and toxic effects of 4-hydroxycoumarin in a preclinical mouse melanoma model. Cancer Chemother. Pharmacol. 2010 65 5 931 940 10.1007/s00280‑009‑1100‑z 19690859
    [Google Scholar]
  84. Ebrahimi S. Mostafavi-Pour Z. Khazaei M. Nazari S.E. Jamshidi S.T. Soukhtanloo M. Suppression of metastasis by citrus auraptene in a mouse model of colorectal cancer. Rev. Bras. Farmacogn. 2023 33 1 182 190 10.1007/s43450‑022‑00351‑w
    [Google Scholar]
  85. Feng H. Lu J.J. Wang Y. Pei L. Chen X. Osthole inhibited TGF β -induced epithelial–mesenchymal transition (EMT) by suppressing NF-κB mediated Snail activation in lung cancer A549 cells. Cell Adhes. Migr. 2017 11 5-6 464 475 10.1080/19336918.2016.1259058 28146373
    [Google Scholar]
  86. Wen Y.C. Lee W.J. Tan P. Yang S.F. Hsiao M. Lee L.M. Chien M.H. By inhibiting snail signaling and miR-23a-3p, osthole suppresses the EMT-mediated metastatic ability in prostate cancer. Oncotarget 2015 6 25 21120 21136 10.18632/oncotarget.4229 26110567
    [Google Scholar]
  87. Wu C. Sun Z. Guo B. Ye Y. Han X. Qin Y. Liu S. Osthole inhibits bone metastasis of breast cancer. Oncotarget 2017 8 35 58480 58493 10.18632/oncotarget.17024 28938572
    [Google Scholar]
  88. Fukuda H. Nakamura S. Chisaki Y. Takada T. Toda Y. Murata H. Itoh K. Yano Y. Takata K. Ashihara E. Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression. Biochem. Biophys. Res. Commun. 2016 471 1 63 67 10.1016/j.bbrc.2016.01.179 26845352
    [Google Scholar]
  89. Kim W.K. Byun W.S. Chung H.J. Oh J. Park H.J. Choi J.S. Lee S.K. Esculetin suppresses tumor growth and metastasis by targeting Axin2/E-cadherin axis in colorectal cancer. Biochem. Pharmacol. 2018 152 71 83 10.1016/j.bcp.2018.03.009 29534875
    [Google Scholar]
  90. Yao D. Pan D. Zhen Y. Huang J. Wang J. Zhang J. He Z. Ferulin C triggers potent PAK1 and p21-mediated anti-tumor effects in breast cancer by inhibiting Tubulin polymerization in vitro and in vivo. Pharmacol. Res. 2020 152 104605 10.1016/j.phrs.2019.104605 31863866
    [Google Scholar]
  91. Yu C.L. Yu Y.L. Yang S.F. Hsu C.E. Lin C.L. Hsieh Y.H. Chiou H.L. Praeruptorin A reduces metastasis of human hepatocellular carcinoma cells by targeting ERK / MMP1 signaling pathway. Environ. Toxicol. 2021 36 4 540 549 10.1002/tox.23059 33226171
    [Google Scholar]
  92. Vitale D.L. Icardi A. Rosales P. Spinelli F.M. Sevic I. Alaniz L.D. Targeting the tumor extracellular matrix by the natural molecule 4-Methylumbelliferone: A complementary and alternative cancer therapeutic strategy. Front. Oncol. 2021 11 710061 10.3389/fonc.2021.710061 34676159
    [Google Scholar]
  93. Wang T.P. Pan Y.R. Fu C.Y. Chang H.Y. Down-regulation of UDP-glucose dehydrogenase affects glycosaminoglycans synthesis and motility in HCT-8 colorectal carcinoma cells. Exp. Cell Res. 2010 316 17 2893 2902 10.1016/j.yexcr.2010.07.017 20691680
    [Google Scholar]
  94. Wróblewska-Łuczka P. Grabarska A. Góralczyk A. Marzęda P. Łuszczki J.J. Fraxetin interacts additively with cisplatin and mitoxantrone, antagonistically with docetaxel in various human melanoma cell lines—An isobolographic analysis. Int. J. Mol. Sci. 2022 24 1 212 10.3390/ijms24010212 36613654
    [Google Scholar]
  95. Kimura Y. Sumiyoshi M. Antitumor and antimetastatic actions of dihydroxycoumarins (esculetin or fraxetin) through the inhibition of M2 macrophage differentiation in tumor-associated macrophages and/or G1 arrest in tumor cells. Eur. J. Pharmacol. 2015 746 115 125 10.1016/j.ejphar.2014.10.048 25445053
    [Google Scholar]
  96. Alizadeh N.M. Rashidi M. Muhammadnejad A. Moeini Zanjani T. Ziai S.A. Antitumor effects of umbelliprenin in a mouse model of colorectal cancer. Iran. J. Pharm. Res. 2018 17 3 976 985 [PMID: 30127820
    [Google Scholar]
  97. Rashidi M. Khalilnezhad A. Amani D. Jamshidi H. Muhammadnejad A. Bazi A. Ziai S.A. Umbelliprenin shows antitumor, antiangiogenesis, antimetastatic, anti‐inflammatory, and immunostimulatory activities in 4T1 tumor‐bearing Balb/c mice. J. Cell. Physiol. 2018 233 11 8908 8918 10.1002/jcp.26814 29797576
    [Google Scholar]
  98. Ko J.H. Nam D. Um J.Y. Jung S. Sethi G. Ahn K. Bergamottin suppresses metastasis of lung cancer cells through abrogation of diverse oncogenic signaling cascades and epithelial-to-mesenchymal transition. Molecules 2018 23 7 1601 10.3390/molecules23071601 30004418
    [Google Scholar]
  99. Karamysheva A.F. Mechanisms of angiogenesis. Biochemistry 2008 73 7 751 762 10.1134/S0006297908070031 18707583
    [Google Scholar]
  100. Yoo S.Y. Kwon S.M. Angiogenesis and its therapeutic opportunities. Mediators Inflamm. 2013 2013 1 11 10.1155/2013/127170 23983401
    [Google Scholar]
  101. Klein G. Vellenga E. Fraaije M.W. Kamps W.A. de Bont E.S.J.M. The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit. Rev. Oncol. Hematol. 2004 50 2 87 100 10.1016/j.critrevonc.2003.09.001 15157658
    [Google Scholar]
  102. Majnooni M.B. Fakhri S. Smeriglio A. Trombetta D. Croley C.R. Bhattacharyya P. Sobarzo-Sánchez E. Farzaei M.H. Bishayee A. Antiangiogenic effects of coumarins against cancer: From chemistry to medicine. Molecules 2019 24 23 4278 10.3390/molecules24234278 31771270
    [Google Scholar]
  103. Charmforoshan E. Karimi E. Oskoueian E. Es-Haghi A. Iranshahi M. Inhibition of human breast cancer cells (MCF-7 cell line) growth via cell proliferation, migration, and angiogenesis by auraptene of Ferula szowitsiana root extract. J. Food Meas. Charact. 2019 13 4 2644 2653 10.1007/s11694‑019‑00185‑6
    [Google Scholar]
  104. Jamialahmadi K. Salari S. Alamolhodaei N.S. Avan A. Gholami L. Karimi G. Auraptene inhibits migration and invasion of cervical and ovarian cancer cells by repression of matrix metalloproteinasas 2 and 9 activity. J. Pharmacopuncture 2018 21 3 177 184 10.3831/KPI.2018.21.021 30283705
    [Google Scholar]
  105. Shiran M.R. Mahmoudian E. Ajami A. Hosseini S.M. Khojasteh A. Rashidi M. Maroufi N.F. Effect of Auraptene on angiogenesis in Xenograft model of breast cancer. Horm. Mol. Biol. Clin. Investig. 2022 43 1 7 14 10.1515/hmbci‑2021‑0056 34851565
    [Google Scholar]
  106. Hosseini F. Ahmadi A. Hassanzade H. Gharedaghi S. Rassouli F.B. Jamialahmadi K. Inhibition of melanoma cell migration and invasion by natural coumarin auraptene through regulating EMT markers and reducing MMP-2 and MMP-9 activity. Eur. J. Pharmacol. 2024 971 176517 10.1016/j.ejphar.2024.176517 38537805
    [Google Scholar]
  107. Ying T.H. Lin C.L. Chen P.N. Wu P.J. Liu C.J. Hsieh Y.H. Angelol-A exerts anti-metastatic and anti-angiogenic effects on human cervical carcinoma cells by modulating the phosphorylated-ERK/miR-29a-3p that targets the MMP2/VEGFA axis. Life Sci. 2022 296 120317 10.1016/j.lfs.2022.120317 35026214
    [Google Scholar]
  108. Son S.H. Kim M.J. Chung W.Y. Son J.A. Kim Y.S. Kim Y.C. Kang S.S. Lee S.K. Park K.K. Decursin and decursinol inhibit VEGF-induced angiogenesis by blocking the activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase. Cancer Lett. 2009 280 1 86 92 10.1016/j.canlet.2009.02.012 19307054
    [Google Scholar]
  109. Jung M.H. Lee S.H. Ahn E.M. Lee Y.M. Decursin and decursinol angelate inhibit VEGF-induced angiogenesis via suppression of the VEGFR-2-signaling pathway. Carcinogenesis 2009 30 4 655 661 10.1093/carcin/bgp039 19228635
    [Google Scholar]
  110. Rafatpanah H. Golizadeh M. Mahdifar M. Mahdavi S. Iranshahi M. Rassouli F.B. Conferone, a coumarin from Ferula flabelliloba, induced toxic effects on adult T-cell leukemia/lymphoma cells. Int. J. Immunopathol. Pharmacol. 2023 37 03946320231197592 10.1177/03946320231197592 37688389
    [Google Scholar]
  111. Cheraghi O. Dehghan G. Mahdavi M. Rahbarghazi R. Rezabakhsh A. Charoudeh H.N. Iranshahi M. Montazersaheb S. Potent anti-angiogenic and cytotoxic effect of conferone on human colorectal adenocarcinoma HT-29 cells. Phytomedicine 2016 23 4 398 405 10.1016/j.phymed.2016.01.015 27002410
    [Google Scholar]
  112. Pan R. Dai Y. Gao X.H. Lu D. Xia Y.F. Inhibition of vascular endothelial growth factor-induced angiogenesis by scopoletin through interrupting the autophosphorylation of VEGF receptor 2 and its downstream signaling pathways. Vascul. Pharmacol. 2011 54 1-2 18 28 10.1016/j.vph.2010.11.001 21078410
    [Google Scholar]
  113. Lee J.H. Choi S. Lee Y. Lee H.J. Kim K.H. Ahn K.S. Bae H. Lee H.J. Lee E.O. Ahn K.S. Ryu S.Y. Lü J. Kim S.H. Herbal compound farnesiferol C exerts antiangiogenic and antitumor activity and targets multiple aspects of VEGFR1 (Flt1) or VEGFR2 (Flk1) signaling cascades. Mol. Cancer Ther. 2010 9 2 389 399 10.1158/1535‑7163.MCT‑09‑0775 20103598
    [Google Scholar]
  114. Kumar A. Sunita P. Jha S. Pattanayak S.P. Daphnetin inhibits TNF-α and VEGF-induced angiogenesis through inhibition of the IKKs/IκBα/NF-κB, Src/FAK/ERK1/2 and Akt signalling pathways. Clin. Exp. Pharmacol. Physiol. 2016 43 939 950 10.1111/1440‑1681.12608 27297262
    [Google Scholar]
  115. Zhang L. Si J. Li G. Li X. Zhang L. Gao L. Huo X. Liu D. Sun X. Cao L. Umbelliprenin and lariciresinol isolated from a long-term-used herb medicine Ferula sinkiangensis induce apoptosis and G0/G1 arresting in gastric cancer cells. RSC Advances 2015 5 110 91006 91017 10.1039/C5RA11335K
    [Google Scholar]
  116. Kim J.H. Kim J.K. Ahn E.K. Ko H.J. Cho Y.R. Lee C.H. Kim Y.K. Bae G.U. Oh J.S. Seo D.W. Marmesin is a novel angiogenesis inhibitor: Regulatory effect and molecular mechanism on endothelial cell fate and angiogenesis. Cancer Lett. 2015 369 2 323 330 10.1016/j.canlet.2015.09.021 26455771
    [Google Scholar]
  117. Yao F. Zhang L. Jiang G. Liu M. Liang G. Yuan Q. Osthole attenuates angiogenesis in an orthotopic mouse model of hepatocellular carcinoma via the downregulation of nuclear factor κB and vascular endothelial growth factor. Oncol. Lett. 2018 16 4 4471 4479 10.3892/ol.2018.9213 30214582
    [Google Scholar]
  118. Raji E. Vahedian V. Golshanrad P. Nahavandi R. Behshood P. Soltani N. Gharibi M. Rashidi M. Maroufi N.F. The potential therapeutic effects of Galbanic acid on cancer. Pathol. Res. Pract. 2023 248 154686 10.1016/j.prp.2023.154686 37487315
    [Google Scholar]
  119. Kim K.H. Lee H.J. Jeong S.J. Lee H.J. Lee E.O. Kim H.S. Zhang Y. Ryu S.Y. Lee M.H. Lü J. Kim S.H. Galbanic acid isolated from Ferula assafoetida exerts in vivo anti-tumor activity in association with anti-angiogenesis and anti-proliferation. Pharm. Res. 2011 28 3 597 609 10.1007/s11095‑010‑0311‑7 21063754
    [Google Scholar]
  120. Wu L. Wang X. Xu W. Farzaneh F. Xu R. The structure and pharmacological functions of coumarins and their derivatives. Curr. Med. Chem. 2009 16 32 4236 4260 10.2174/092986709789578187 19754420
    [Google Scholar]
  121. Lopez-Gonzalez J.S. Prado-Garcia H. Aguilar-Cazares D. Molina-Guarneros J.A. Morales-Fuentes J. Mandoki J.J. Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines. Lung Cancer 2004 43 3 275 283 10.1016/j.lungcan.2003.09.005 15165085
    [Google Scholar]
  122. Haghighitalab A. Matin M.M. Bahrami A.R. Iranshahi M. Saeinasab M. Haghighi F. In vitro investigation of anticancer, cell-cycle-inhibitory, and apoptosis-inducing effects of diversin, a natural prenylated coumarin, on bladder carcinoma cells. Z. Naturforsch. C J. Biosci. 2014 69 3-4 99 109 10.5560/znc.2013‑0006 24873030
    [Google Scholar]
  123. Turkekul K. Colpan R.D. Baykul T. Ozdemir M.D. Erdogan S. Esculetin inhibits the survival of human prostate cancer cells by inducing apoptosis and arresting the cell cycle. J. Cancer Prev. 2018 23 1 10 17 10.15430/JCP.2018.23.1.10 29629344
    [Google Scholar]
  124. Rasul A. Khan M. Yu B. Ma T. Yang H. Xanthoxyletin, a coumarin induces S phase arrest and apoptosis in human gastric adenocarcinoma SGC-7901 cells. Asian Pac. J. Cancer Prev. 2011 12 5 1219 1223 [PMID: 21875271
    [Google Scholar]
  125. Tian Q. Wang L. Sun X. Zeng F. Pan Q. Xue M. Scopoletin exerts anticancer effects on human cervical cancer cell lines by triggering apoptosis, cell cycle arrest, inhibition of cell invasion and PI3K/AKT signalling pathway. J. BUON 2019 24 3 997 1002 [PMID: 31424653
    [Google Scholar]
  126. Chao X. Zhou X. Zheng G. Dong C. Zhang W. Song X. Jin T. Osthole induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Pharm. Biol. 2014 52 5 544 550 10.3109/13880209.2013.850517 24236568
    [Google Scholar]
  127. Sethi A. Munagalasetty S. Arifuddin M. Carradori S. Supuran C.T. Alvala R. Alvala M. Coumarin and piperazine conjugates as selective inhibitors of the tumor-associated carbonic Anhydrase IX and XII isoforms. Anticancer. Agents Med. Chem. 2023 23 10 1184 1191 10.2174/1871520623666230202123535 36733240
    [Google Scholar]
  128. Redij A. Carradori S. Petreni A. Supuran C.T. Toraskar M.P. Coumarin-pyrazoline hybrids as selective inhibitors of the tumor-associated carbonic anhydrase IX and XII. Anticancer. Agents Med. Chem. 2023 23 10 1217 1223 10.2174/1871520623666230220162506 36825712
    [Google Scholar]
  129. Ozensoy Guler O. Supuran C.T. Capasso C. Carbonic anhydrase IX as a novel candidate in liquid biopsy. J. Enzyme Inhib. Med. Chem. 2020 35 1 255 260 10.1080/14756366.2019.1697251 31790601
    [Google Scholar]
  130. McIntyre A. Harris A.L. The role of pH regulation in cancer progression. Recent Results Cancer Res. 2016 ••• 93 134 10.1007/978‑3‑319‑42118‑6_5
    [Google Scholar]
  131. Supuran C.T. Carbonic anhydrase inhibitors and their potential in a range of therapeutic areas. Expert Opin. Ther. Pat. 2018 28 10 709 712 10.1080/13543776.2018.1523897 30217119
    [Google Scholar]
  132. Doyen J. Parks S.K. Marcié S. Pouysségur J. Chiche J. Knock-down of hypoxia-induced carbonic anhydrases IX and XII radiosensitizes tumor cells by increasing intracellular acidosis. Front. Oncol. 2013 2 199 10.3389/fonc.2012.00199 23316475
    [Google Scholar]
  133. Kallio H. Pastorekova S. Pastorek J. Waheed A. Sly W.S. Mannisto S. Heikinheimo M. Parkkila S. Expression of carbonic anhydrases IX and XII during mouse embryonic development. BMC Dev. Biol. 2006 6 1 22 10.1186/1471‑213X‑6‑22 16719910
    [Google Scholar]
  134. Supuran C.T. Coumarin carbonic anhydrase inhibitors from natural sources. J. Enzyme Inhib. Med. Chem. 2020 35 1 1462 1470 10.1080/14756366.2020.1788009 32779543
    [Google Scholar]
  135. Vu H. Pham N.B. Quinn R.J. Direct screening of natural product extracts using mass spectrometry. SLAS Discov. 2008 13 4 265 275 10.1177/1087057108315739 18349420
    [Google Scholar]
  136. Maresca A. Temperini C. Vu H. Pham N.B. Poulsen S.A. Scozzafava A. Quinn R.J. Supuran C.T. Non-zinc mediated inhibition of carbonic anhydrases: Coumarins are a new class of suicide inhibitors. J. Am. Chem. Soc. 2009 131 8 3057 3062 10.1021/ja809683v 19206230
    [Google Scholar]
  137. Davis R.A. Vullo D. Maresca A. Supuran C.T. Poulsen S.A. Natural product coumarins that inhibit human carbonic anhydrases. Bioorg. Med. Chem. 2013 21 6 1539 1543 10.1016/j.bmc.2012.07.021 22892213
    [Google Scholar]
  138. Fois B. Distinto S. Meleddu R. Deplano S. Maccioni E. Floris C. Rosa A. Nieddu M. Caboni P. Sissi C. Angeli A. Supuran C.T. Cottiglia F. Coumarins from Magydaris pastinacea as inhibitors of the tumour-associated carbonic anhydrases IX and XII: Isolation, biological studies and in silico evaluation. J. Enzyme Inhib. Med. Chem. 2020 35 1 539 548 10.1080/14756366.2020.1713114 31948300
    [Google Scholar]
  139. Touisni N. Maresca A. McDonald P.C. Lou Y. Scozzafava A. Dedhar S. Winum J.Y. Supuran C.T. Glycosyl coumarin carbonic anhydrase IX and XII inhibitors strongly attenuate the growth of primary breast tumors. J. Med. Chem. 2011 54 24 8271 8277 10.1021/jm200983e 22077347
    [Google Scholar]
  140. Lou Y. McDonald P.C. Oloumi A. Chia S. Ostlund C. Ahmadi A. Kyle A. auf dem Keller U. Leung S. Huntsman D. Clarke B. Sutherland B.W. Waterhouse D. Bally M. Roskelley C. Overall C.M. Minchinton A. Pacchiano F. Carta F. Scozzafava A. Touisni N. Winum J.Y. Supuran C.T. Dedhar S. Targeting tumor hypoxia: Suppression of breast tumor growth and metastasis by novel carbonic anhydrase IX inhibitors. Cancer Res. 2011 71 9 3364 3376 10.1158/0008‑5472.CAN‑10‑4261 21415165
    [Google Scholar]
  141. Sever R. Brugge J.S. Signal transduction in cancer. Cold Spring Harb. Perspect. Med. 2015 5 4 a006098 a006098 10.1101/cshperspect.a006098 25833940
    [Google Scholar]
  142. Hashem S. Ali T.A. Akhtar S. Nisar S. Sageena G. Ali S. Al-Mannai S. Therachiyil L. Mir R. Elfaki I. Mir M.M. Jamal F. Masoodi T. Uddin S. Singh M. Haris M. Macha M. Bhat A.A. Targeting cancer signaling pathways by natural products: Exploring promising anti-cancer agents. Biomed. Pharmacother. 2022 150 113054 10.1016/j.biopha.2022.113054 35658225
    [Google Scholar]
  143. Zlobin A. Bloodworth J.C. Osipo C. Mitogen-Activated Protein Kinase (MAPK) Signaling Predict Biomarkers Oncol. Cham Springer International Publishing 2019 213 221 10.1007/978‑3‑319‑95228‑4_16
    [Google Scholar]
  144. Li L. Zhao G.D. Shi Z. Qi L.L. Zhou L.Y. Fu Z.X. The Ras/Raf/MEK/ERK signaling pathway and its role in the occurrence and development of HCC. Oncol. Lett. 2016 12 5 3045 3050 10.3892/ol.2016.5110 27899961
    [Google Scholar]
  145. Burotto M. Chiou V.L. Lee J.M. Kohn E.C. The MAPK pathway across different malignancies: A new perspective. Cancer 2014 120 22 3446 3456 10.1002/cncr.28864 24948110
    [Google Scholar]
  146. Rostom B. Karaky R. Kassab I. Sylla-Iyarreta Veitía M. Coumarins derivatives and inflammation: Review of their effects on the inflammatory signaling pathways. Eur. J. Pharmacol. 2022 922 174867 10.1016/j.ejphar.2022.174867 35248553
    [Google Scholar]
  147. Kang J.K. Chung Y.C. Hyun C.G. Anti-inflammatory effects of 6-Methylcoumarin in LPS-Stimulated RAW 264.7 Macrophages via regulation of MAPK and NF-κB signaling pathways. Molecules 2021 26 17 5351 10.3390/molecules26175351 34500784
    [Google Scholar]
  148. Lee N. Chung Y.C. Kim Y.B. Park S-M. Kim B.S. Hyun C-G. 7,8-Dimethoxycoumarin stimulates melanogenesis via MAPKs mediated MITF upregulation. Pharmazie 2020 75 2 107 111 10.1691/ph.2020.9735 32213243
    [Google Scholar]
  149. Yang J. Nie J. Ma X. Wei Y. Peng Y. Wei X. Targeting PI3K in cancer: Mechanisms and advances in clinical trials. Mol. Cancer 2019 18 1 26 10.1186/s12943‑019‑0954‑x 30782187
    [Google Scholar]
  150. Shi X. Wang J. Lei Y. Cong C. Tan D. Zhou X. Research progress on the PI3K/AKT signaling pathway in gynecological cancer (Review). Mol. Med. Rep. 2019 19 6 4529 4535 10.3892/mmr.2019.10121 30942405
    [Google Scholar]
  151. Pópulo H. Lopes J.M. Soares P. The mTOR signalling pathway in human cancer. Int. J. Mol. Sci. 2012 13 2 1886 1918 10.3390/ijms13021886 22408430
    [Google Scholar]
  152. Saxton R.A. Sabatini D.M. mTOR signaling in growth, metabolism, and disease. Cell 2017 168 6 960 976 10.1016/j.cell.2017.02.004 28283069
    [Google Scholar]
  153. Yang J. Zhu X. Jin M. Cao Z. Ren Y. Gu Z. Osthole induces cell cycle arrest and apoptosis in head and neck squamous cell carcinoma by suppressing the PI3K/AKT signaling pathway. Chem. Biol. Interact. 2020 316 108934 10.1016/j.cbi.2019.108934 31870840
    [Google Scholar]
  154. Ding D. Wei S. Song Y. Li L. Du G. Zhan H. Cao Y. Osthole exhibits anti-cancer property in rat glioma cells through inhibiting PI3K/Akt and MAPK signaling pathways. Cell. Physiol. Biochem. 2013 32 6 1751 1760 10.1159/000356609 24356539
    [Google Scholar]
  155. Guo H. He Y. Bu C. Peng Z. Antitumor and apoptotic effects of 5-methoxypsoralen in U87MG human glioma cells and its effect on cell cycle, autophagy and PI3K/Akt signaling pathway. Arch. Med. Sci. 2019 15 6 1530 1538 10.5114/aoms.2019.81729 31749882
    [Google Scholar]
  156. Wang Q. Zhong S. Wu H. Wu Q. In vitro anti-cancer effect of marmesin by suppression of PI3K/Akt pathway in esophagus cancer cells. Esophagus 2022 19 1 163 174 10.1007/s10388‑021‑00872‑8 34398363
    [Google Scholar]
  157. Tafani M. Pucci B. Russo A. Schito L. Pellegrini L. Perrone G.A. Villanova L. Salvatori L. Ravenna L. Petrangeli E. Russo M.A. Modulators of HIF1α and NFkB in cancer treatment: Is it a rational approach for controlling malignant progression? Front. Pharmacol. 2013 4 13 10.3389/fphar.2013.00013 23408731
    [Google Scholar]
  158. Hayden M.S. Ghosh S. Shared principles in NF-kappaB signaling. Cell 2008 132 3 344 362 10.1016/j.cell.2008.01.020 18267068
    [Google Scholar]
  159. Kao S.J. Su J.L. Chen C.K. Yu M.C. Bai K.J. Chang J.H. Bien M.Y. Yang S.F. Chien M.H. Osthole inhibits the invasive ability of human lung adenocarcinoma cells via suppression of NF-κB-mediated matrix metalloproteinase-9 expression. Toxicol. Appl. Pharmacol. 2012 261 1 105 115 10.1016/j.taap.2012.03.020 22503731
    [Google Scholar]
  160. Che Y. Li J. Li Z. Li J. Wang S. Yan Y. Zou K. Zou L. Osthole enhances antitumor activity and irradiation sensitivity of cervical cancer cells by suppressing ATM/NF κB signaling. Oncol. Rep. 2018 40 2 737 747 10.3892/or.2018.6514 29989651
    [Google Scholar]
  161. Kim S.M. Lee E.J. Lee J.H. Yang W.M. Nam D. Lee J.H. Lee S.G. Um J.Y. Shim B.S. Ahn K.S. Simvastatin in combination with bergamottin potentiates TNF-induced apoptosis through modulation of NF-κB signalling pathway in human chronic myelogenous leukaemia. Pharm. Biol. 2016 54 10 2050 2060 10.3109/13880209.2016.1141221 26911804
    [Google Scholar]
  162. Wang Y. Li C.F. Pan L.M. Gao Z.L. 7,8-Dihydroxycoumarin inhibits A549 human lung adenocarcinoma cell proliferation by inducing apoptosis via suppression of Akt/NF-κB signaling. Exp. Ther. Med. 2013 5 6 1770 1774 10.3892/etm.2013.1054 23837071
    [Google Scholar]
  163. Brooks A.J. Putoczki T. JAK-STAT signalling pathway in cancer. Cancers 2020 12 7 1971 10.3390/cancers12071971 32698360
    [Google Scholar]
  164. Dutta P. Li W.X. Role of the JAK‐STAT Signalling Pathway in Cancer Encycl Life. Sci. Wiley 2013 10.1002/9780470015902.a0025214
    [Google Scholar]
  165. Kim S.M. Lee J.H. Sethi G. Kim C. Baek S.H. Nam D. Chung W.S. Kim S.H. Shim B.S. Ahn K.S. Bergamottin, a natural furanocoumarin obtained from grapefruit juice induces chemosensitization and apoptosis through the inhibition of STAT3 signaling pathway in tumor cells. Cancer Lett. 2014 354 1 153 163 10.1016/j.canlet.2014.08.002 25130169
    [Google Scholar]
  166. Peng L. Huang X. Jin X. Jing Z. Yang L. Zhou Y. Ren J. Zhao Y. Wedelolactone, a plant coumarin, prevents vascular smooth muscle cell proliferation and injury-induced neointimal hyperplasia through Akt and AMPK signaling. Exp. Gerontol. 2017 96 73 81 10.1016/j.exger.2017.06.011 28634089
    [Google Scholar]
  167. Perri M.R. Pellegrino M. Aquaro S. Cavaliere F. Lupia C. Uzunov D. Marrelli M. Conforti F. Statti G. Cachrys spp. from Southern Italy: Phytochemical Characterization and JAK/STAT Signaling Pathway Inhibition. Plants 2022 11 21 2913 10.3390/plants11212913 36365365
    [Google Scholar]
  168. Kim J.K. Kim J.Y. Kim H.J. Park K.G. Harris R.A. Cho W.J. Lee J.T. Lee I.K. Scoparone exerts anti-tumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity. PLoS One 2013 8 11 e80391 10.1371/journal.pone.0080391 24260381
    [Google Scholar]
  169. Xiong W. Dong J. Kong S. Dentatin exerts anticancer effects on human colon cancer cell lines via cell cycle arrest, autophagy, inhibition of cell migration and JAK/STAT signalling pathway. J. BUON 2019 24 4 1488 1493 [PMID: 31646796
    [Google Scholar]
  170. Qu L. Lin P. Lin M. Ye S. Papa Akuetteh P.D. Zhu Y. Fraxetin Inhibits the Proliferation and Metastasis of Glioma Cells by Inactivating JAK2/STAT3 Signaling. Evid. Based Complement. Alternat. Med. 2021 2021 1 10 10.1155/2021/5540139 33959183
    [Google Scholar]
  171. Zhan T. Rindtorff N. Boutros M. Wnt signaling in cancer. Oncogene 2017 36 11 1461 1473 10.1038/onc.2016.304 27617575
    [Google Scholar]
  172. Katoh M. Katoh M. WNT signaling pathway and stem cell signaling network. Clin. Cancer Res. 2007 13 14 4042 4045 10.1158/1078‑0432.CCR‑06‑2316 17634527
    [Google Scholar]
  173. Taciak B. Pruszynska I. Kiraga L. Bialasek M. Krol M. Wnt signaling pathway in development and cancer. J. Physiol. Pharmacol. 2018 69 2 185 196 10.26402/jpp.2018.2.07 29980141
    [Google Scholar]
  174. Lee S.Y. Lim T.G. Chen H. Jung S.K. Lee H.J. Lee M.H. Kim D.J. Shin A. Lee K.W. Bode A.M. Surh Y.J. Dong Z. Esculetin suppresses proliferation of human colon cancer cells by directly targeting β-catenin. Cancer Prev. Res 2013 6 12 1356 1364 10.1158/1940‑6207.CAPR‑13‑0241 24104353
    [Google Scholar]
  175. Zhang L. Sun X. Si J. Li G. Cao L. Umbelliprenin isolated from Ferula sinkiangensis inhibits tumor growth and migration through the disturbance of Wnt signaling pathway in gastric cancer. PLoS One 2019 14 7 e0207169 10.1371/journal.pone.0207169 31260453
    [Google Scholar]
  176. Li T. Zhang L. Huo X. Inhibitory effects of aesculetin on the proliferation of colon cancer cells by the Wnt/β-catenin signaling pathway. Oncol. Lett. 2018 15 5 7118 7122 10.3892/ol.2018.8244 29725434
    [Google Scholar]
  177. Song G.Y. Lee J.H. Cho M. Park B.S. Kim D.E. Oh S. Decursin suppresses human androgen-independent PC3 prostate cancer cell proliferation by promoting the degradation of β-catenin. Mol. Pharmacol. 2007 72 6 1599 1606 10.1124/mol.107.040253 17855653
    [Google Scholar]
  178. Thornes R.D. Daly L. Lynch G. Breslin B. Browne H. Browne H.Y. Corrigan T. Daly P. Edwards G. Gaffney E. Henley J. Healy T. Keane F. Lennon F. McMurray N. O’Loughlin S. Shine M. Tanner A. Treatment with coumarin to prevent or delay recurrence of malignant melanoma. J. Cancer Res. Clin. Oncol. 1994 120 S1 S32 S34 [Suppl. 10.1007/BF01377122 8132701
    [Google Scholar]
  179. Dexeus F.H. Logothetis C.J. Sella A. Fitz K. Amato R. Reuben J.M. Dozier N. Phase II study of coumarin and cimetidine in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 1990 8 2 325 329 10.1200/JCO.1990.8.2.325 2137163
    [Google Scholar]
  180. Grötz K.A. Wüstenberg P. Kohnen R. Al-Nawas B. Henneicke-von Zepelin H.H. Bockisch A. Kutzner J. Naser-Hijazi B. Belz G.G. Wagner W. Prophylaxis of radiogenic sialadenitis and mucositis by coumarin/troxerutine in patients with head and neck cancer – A prospective,randomized, placebo-controlled, double-blind study. Br. J. Oral Maxillofac. Surg. 2001 39 1 34 39 10.1054/bjom.2000.0459 11178853
    [Google Scholar]
  181. Zacharski L.R. Henderson W.G. Rickles F.R. Forman W.B. Cornell C.J. Forcier R.J. Edwards R. Headley E. Kim S.H. O’Donnell J.R. O’Dell R. Tornyos K. Kwaan H.C. Effect of warfarin on survival in small cell carcinoma of the lung. Veterans Administration Study No. 75. JAMA 1981 245 8 831 835 10.1001/jama.1981.03310330021017 6257941
    [Google Scholar]
  182. Haaland G.S. Falk R.S. Straume O. Lorens J.B. Association of warfarin use with lower overall cancer incidence among patients older than 50 years. JAMA Intern. Med. 2017 177 12 1774 1780 10.1001/jamainternmed.2017.5512 29114736
    [Google Scholar]
  183. Shaheen H.M. Nyemb J.N. Segueni N. George J. Patil R. V.; El-Saber Batiha, G. Anticancer properties and clinical trials of coumarins: A review. Free Radic. Antioxid. 2022 12 2 41 48 10.5530/fra.2022.2.8
    [Google Scholar]
/content/journals/acamc/10.2174/0118715206385367250610045200
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Exploring Natural Coumarins: Breakthroughs in Anticancer Therapeutics
Bentham Science Publishers ; https://doi.org/10.2174/0118715206385367250610045200
/content/journals/acamc/10.2174/0118715206385367250610045200
/content/journals/acamc/10.2174/0118715206385367250610045200
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  • Article Type:     Review Article
Keywords: cancer ; Anticancer ; natural coumarins ; Apoptosis ; natural products ; cell cycle

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