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2000
Volume 32, Issue 34
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Recently, increasing attention has been directed toward nutraceuticals, natural substances extracted from plants, fruits, or cereals. These compounds are well-known for their antibacterial, anti-inflammatory, antioxidant, and antitumor properties, with the latter being the primary focus of this review. The use of nutraceuticals, both as standalone treatments and in combination with standard chemotherapy, has been extensively studied through , experiments, and clinical trials for the prevention and treatment of various types of cancer, including breast, colon, pancreatic, prostate cancers, and leukemia. Findings from these studies emphasize the benefits of nutraceuticals in improving patient compliance and mitigating the adverse effects of conventional drugs. Specifically, the combination of nutraceuticals with chemotherapy allows for reduced dosages of synthetic drugs, thereby lessening their often-severe side effects. In this review, we explore the diverse mechanisms of action underlying the antitumor activity of key nutraceuticals-including curcumin, resveratrol, tocotrienols, ursolic acid, fisetin, gambogic acid, catechins, silibinin, berberine, emodin, piperine, deguelin, garcinol, plumbagin, zerumbone, and ginger. Furthermore, we summarize the most significant outcomes from clinical trials investigating these compounds. The clinical studies addressed various aspects of treatment, such as efficacy, safety, maximum tolerated doses, potential adverse effects, and patient compliance. The majority of the findings highlight the positive impact of combining nutraceuticals with chemotherapy, demonstrating enhanced therapeutic outcomes in anticancer treatments.

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2025-10-31
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References

  1. CalvaniM. PashaA. FavreC. Nutraceutical boom in cancer: Inside the labyrinth of reactive oxygen species.Int. J. Mol. Sci.2020216193610.3390/ijms2106193632178382
    [Google Scholar]
  2. The NutraCeutical Revolution: Fueling a Powerful, New International Market. Available from: https://fimdefelice.org/library/the-nutraceutical-revolution-fueling-a-powerful-new-international-market/ (Accessed on June 22, 2024).
  3. SantiniA. TenoreG.C. NovellinoE. Nutraceuticals: A paradigm of proactive medicine.Eur. J. Pharm. Sci.201796536110.1016/j.ejps.2016.09.00327613382
    [Google Scholar]
  4. JainN. Nutraceuticals and Antioxidants in Prevention of Diseases.Natural Products: Phytochemistry, botany and metabolism of alkaloids, phenolics and terpenes. RamawatK.G. MérillonJ-M. Springer Berlin Heidelberg20132559258010.1007/978‑3‑642‑22144‑6_70
    [Google Scholar]
  5. PrakashD. GuptaC. SharmaG. Importance of phytochemicals in nutraceuticals.J.Chin. Med. Res. Develop.201217078
    [Google Scholar]
  6. ZhengJ. ZhouY. LiY. XuD.P. LiS. LiH.B. Spices for prevention and treatment of cancers.Nutrients20168849510.3390/nu808049527529277
    [Google Scholar]
  7. Institute of Medicine (US) Food and Nutrition BoardDietary Reference Intakes: A Risk Assessment Model for Establishing Upper Intake Levels for Nutrients.National Academies PressWashington (DC)199820845565
    [Google Scholar]
  8. ZhangY.J. GanR.Y. LiS. ZhouY. LiA.N. XuD.P. LiH.B. Antioxidant phytochemicals for the prevention and treatment of chronic diseases.Molecules20152012211382115610.3390/molecules20121975326633317
    [Google Scholar]
  9. Fuchs-TarlovskyV. Role of antioxidants in cancer therapy.Nutrition2013291152110.1016/j.nut.2012.02.01422784609
    [Google Scholar]
  10. KhuranaR.K. JainA. JainA. SharmaT. SinghB. KesharwaniP. Administration of antioxidants in cancer: Debate of the decade.Drug Discov. Today201823476377010.1016/j.drudis.2018.01.02129317341
    [Google Scholar]
  11. SinghK. BhoriM. KasuY.A. BhatG. MararT. Antioxidants as precision weapons in war against cancer chemotherapy induced toxicity: Exploring the armoury of obscurity.Saudi Pharm. J.201826217719010.1016/j.jsps.2017.12.01330166914
    [Google Scholar]
  12. SimoneC.B.II SimoneN.L. SimoneV. SimoneC.B. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, part 1.Altern. Ther. Health Med.2007131222817283738
    [Google Scholar]
  13. BordoloiD. RoyN.K. MonishaJ. PadmavathiG. KunnumakkaraA.B. Multi-targeted agents in cancer cell chemosensitization: What we learnt from Curcumin thus far.Recent Patents Anticancer Drug Discov.2016111679710.2174/157489281066615102010170626537958
    [Google Scholar]
  14. KunnumakkaraA.B. BordoloiD. PadmavathiG. MonishaJ. RoyN.K. PrasadS. AggarwalB.B. Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases.Br. J. Pharmacol.2017174111325134810.1111/bph.1362127638428
    [Google Scholar]
  15. BordoloiD. KunnumakkaraA.B. The potential of curcumin: A multitargeting agent in cancer cell chemosensitization.Role of nutraceuticals in cancer chemosensitization.Academic Press2018316010.1016/B978‑0‑12‑812373‑7.00002‑4
    [Google Scholar]
  16. FialaM. Curcumin and omega-3 fatty acids enhance NK cell-induced apoptosis of pancreatic cancer cells but curcumin inhibits interferon-γ production: Benefits of omega-3 with curcumin against cancer.Molecules20152023020302610.3390/molecules2002302025685909
    [Google Scholar]
  17. QadirM.I. NaqviS.T. MuhammadS.A. Curcumin: A polyphenol with molecular targets for cancer control.Asian Pac. J. Cancer Prev.20161762735273927356682
    [Google Scholar]
  18. TyagiA.K. PrasadS. Molecular targets of curcumin: A potential magic bullet for health.Mol. Biol.20144e123
    [Google Scholar]
  19. SunY. GuanZ. LiangL. ChengY. ZhouJ. LiJ. XuY. NF-κB signaling plays irreplaceable roles in cisplatin-induced bladder cancer chemoresistance and tumor progression.Int. J. Oncol.201648122523410.3892/ijo.2015.325626647959
    [Google Scholar]
  20. KamatA.M. SethiG. AggarwalB.B. Curcumin potentiates the apoptotic effects of chemotherapeutic agents and cytokines through down-regulation of nuclear factor-κB and nuclear factor-κB–regulated gene products in IFN-α–sensitive and IFN-α–resistant human bladder cancer cells.Mol. Cancer Ther.2007631022103010.1158/1535‑7163.MCT‑06‑054517363495
    [Google Scholar]
  21. DilnawazF. SahooS.K. Enhanced accumulation of curcumin and temozolomide loaded magnetic nanoparticles executes profound cytotoxic effect in glioblastoma spheroid model.Eur. J. Pharm. Biopharm.201385345246210.1016/j.ejpb.2013.07.01323891772
    [Google Scholar]
  22. RamachandranC. NairS.M. EscalonE. MelnickS.J. Potentiation of etoposide and temozolomide cytotoxicity by curcumin and turmeric force™ in brain tumor cell lines.J. Complement. Integr. Med.2012912010.1515/1553‑3840.161422944718
    [Google Scholar]
  23. JonesS.K. MerkelO.M. Tackling breast cancer chemoresistance with nano-formulated siRNA.Gene Ther.2016231282182810.1038/gt.2016.6727648580
    [Google Scholar]
  24. GuoQ. LiX. YangY. WeiJ. ZhaoQ. LuoF. QianZ. Enhanced 4T1 breast carcinoma anticancer activity by co-delivery of doxorubicin and curcumin with core-shell drug-carrier based on heparin modified poly(L-lactide) grafted polyethylenimine cationic nanoparticles.J. Biomed. Nanotechnol.201410222723710.1166/jbn.2014.178524738331
    [Google Scholar]
  25. ZhanY. ChenY. LiuR. ZhangH. ZhangY. Potentiation of paclitaxel activity by curcumin in human breast cancer cell by modulating apoptosis and inhibiting EGFR signaling.Arch. Pharm. Res.20143781086109510.1007/s12272‑013‑0311‑324318305
    [Google Scholar]
  26. Bayet-RobertM. KwiatowskiF. LeheurteurM. GachonF. PlanchatE. AbrialC. Mouret-ReynierM.A. DurandoX. BarthomeufC. CholletP. Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer.Cancer Biol. Ther.20109181410.4161/cbt.9.1.1039219901561
    [Google Scholar]
  27. KörberM.I. StaribacherA. RatzenböckI. StegerG. MaderR.M. NFκB-associated pathways in progression of chemoresistance to 5-fluorouracil in an in vitro model colonic carcinoma.Anticancer Res.20163641631163927069140
    [Google Scholar]
  28. YuY. KanwarS.S. PatelB.B. NautiyalJ. SarkarF.H. MajumdarA.P.N. Elimination of colon cancer stem-like cells by the combination of curcumin and FOLFOX.Transl. Oncol.20092432132810.1593/tlo.0919319956394
    [Google Scholar]
  29. PatelB.B. SenguptaR. QaziS. VachhaniH. YuY. RishiA.K. MajumdarA.P.N. Curcumin enhances the effects of 5-fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF-1R.Int. J. Cancer2008122226727310.1002/ijc.2309717918158
    [Google Scholar]
  30. Cruz-CorreaM. ShoskesD.A. SanchezP. ZhaoR. HylindL.M. WexnerS.D. GiardielloF.M. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis.Clin. Gastroenterol. Hepatol.2006481035103810.1016/j.cgh.2006.03.02016757216
    [Google Scholar]
  31. ZhaoL. LiY. SongX. ZhouH. LiN. MiaoY. JiaL. Upregulation of miR-181c inhibits chemoresistance by targeting ST8SIA4 in chronic myelocytic leukemia.Oncotarget2016737600746008610.18632/oncotarget.1105427527856
    [Google Scholar]
  32. ShanmugamM. RaneG. KanchiM. ArfusoF. ChinnathambiA. ZayedM. AlharbiS. TanB. KumarA. SethiG. The multifaceted role of curcumin in cancer prevention and treatment.Molecules20152022728276910.3390/molecules2002272825665066
    [Google Scholar]
  33. FanJ-X. ZengY-J. WuJ-W. LiZ-Q. LiY-M. ZhengR. WengG-Y. GuoK.Y. Synergistic killing effect of arsenic trioxide combined with curcumin on KG1a cells.J. Exp. Hematol.20142251267127225338570
    [Google Scholar]
  34. SánchezY. SimónG.P. CalviñoE. de BlasE. AllerP. Curcumin stimulates reactive oxygen species production and potentiates apoptosis induction by the antitumor drugs arsenic trioxide and lonidamine in human myeloid leukemia cell lines.J. Pharmacol. Exp. Ther.2010335111412310.1124/jpet.110.16834420605902
    [Google Scholar]
  35. WengG. ZengY. HuangJ. FanJ. GuoK. Curcumin enhanced busulfan-induced apoptosis through downregulating the expression of survivin in leukemia stem-like KG1a cells.BioMed Res. Int.2015201511610.1155/2015/63039726557682
    [Google Scholar]
  36. NagyL.I. FehérL.Z. SzebeniG.J. GyurisM. SiposP. AlföldiR. ÓzsváriB. HacklerL.Jr BalázsA. BatárP. KanizsaiI. PuskásL.G. Curcumin and its analogue induce apoptosis in leukemia cells and have additive effects with bortezomib in cellular and xenograft models.BioMed Res. Int.2015201511110.1155/2015/96898126075279
    [Google Scholar]
  37. KimK.C. BaekS.H. LeeC. Curcumin-induced downregulation of Axl receptor tyrosine kinase inhibits cell proliferation and circumvents chemoresistance in non-small lung cancer cells.Int. J. Oncol.20154762296230310.3892/ijo.2015.321626498137
    [Google Scholar]
  38. ChenP. LiJ. JiangH.G. LanT. ChenY.C. Curcumin reverses cisplatin resistance in cisplatin-resistant lung caner cells by inhibiting FA/BRCA pathway.Tumour Biol.20153653591359910.1007/s13277‑014‑2996‑425542235
    [Google Scholar]
  39. ChenP.M. ChengY.W. WuT.C. ChenC.Y. LeeH. MnSOD overexpression confers cisplatin resistance in lung adenocarcinoma via the NF-κB/Snail/Bcl-2 pathway.Free Radic. Biol. Med.20157912713710.1016/j.freeradbiomed.2014.12.00125499851
    [Google Scholar]
  40. LiS. LiuZ. ZhuF. FanX. WuX. ZhaoH. JiangL. Curcumin lowers erlotinib resistance in non-small cell lung carcinoma cells with mutated EGF receptor.Oncol. Res.201421313714410.3727/096504013X1383247333003224512728
    [Google Scholar]
  41. BoztasA.O. KarakuzuO. GalanteG. UgurZ. KocabasF. AltuntasC.Z. YazaydinA.O. Synergistic interaction of paclitaxel and curcumin with cyclodextrin polymer complexation in human cancer cells.Mol. Pharm.20131072676268310.1021/mp400101k23730903
    [Google Scholar]
  42. WengS.H. TsaiM.S. ChiuY.F. KuoY.H. ChenH.J. LinY.W. Enhancement of mitomycin C-induced cytotoxicity by curcumin results from down-regulation of MKK1/2-ERK1/2-mediated thymidine phosphorylase expression.Basic Clin. Pharmacol. Toxicol.2012110329830610.1111/j.1742‑7843.2011.00806.x21973306
    [Google Scholar]
  43. LeeJ.Y. LeeY.M. ChangG.C. YuS.L. HsiehW.Y. ChenJ.J.W. ChenH.W. YangP.C. Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38 activation in intestine: The versatile adjuvant for gefitinib therapy.PLoS One201168e2375610.1371/journal.pone.002375621858220
    [Google Scholar]
  44. PopV.V. SeiceanA. LupanI. SamascaG. BurzC.C. IL-6 roles: Molecular pathway and clinical implication in pancreatic cancer: A systemic review.Immunol. Lett.2017181455010.1016/j.imlet.2016.11.01027876525
    [Google Scholar]
  45. KanaiM. YoshimuraK. AsadaM. ImaizumiA. SuzukiC. MatsumotoS. NishimuraT. MoriY. MasuiT. KawaguchiY. YanagiharaK. YazumiS. ChibaT. GuhaS. AggarwalB.B. A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer.Cancer Chemother. Pharmacol.201168115716410.1007/s00280‑010‑1470‑220859741
    [Google Scholar]
  46. EpelbaumR. SchafferM. VizelB. BadmaevV. Bar-SelaG. Curcumin and gemcitabine in patients with advanced pancreatic cancer.Nutr. Cancer20106281137114110.1080/01635581.2010.51380221058202
    [Google Scholar]
  47. AlshakerH. WangQ. KawanoY. ArafatT. BöhlerT. WinklerM. CooperC. PchejetskiD. Everolimus (RAD001) sensitizes prostate cancer cells to docetaxel by down-regulation of HIF-1α and sphingosine kinase 1.Oncotarget2016749809438095610.18632/oncotarget.1311527821815
    [Google Scholar]
  48. MahammediH. PlanchatE. PougetM. DurandoX. CuréH. GuyL. Van-PraaghI. SavareuxL. AtgerM. Bayet-RobertM. GadeaE. AbrialC. ThivatE. CholletP. EymardJ.C. The new combination docetaxel, prednisone and curcumin in patients with castration-resistant prostate cancer: a pilot phase II study.Oncology2016902697810.1159/00044114826771576
    [Google Scholar]
  49. MohammedS. HarikumarK. B. Role of resveratrol in chemosensitization of cancer.Role of Nutraceuticals in Cancer ChemosensitizationAcademic Press2018617610.1016/B978‑0‑12‑812373‑7.00003‑6
    [Google Scholar]
  50. BuhrmannC. ShayanP. KraeheP. PopperB. GoelA. ShakibaeiM. Resveratrol induces chemosensitization to 5-fluorouracil through up-regulation of intercellular junctions, epithelial-to-mesenchymal transition and apoptosis in colorectal cancer.Biochem. Pharmacol.2015981516810.1016/j.bcp.2015.08.10526310874
    [Google Scholar]
  51. LeeS.H. KooB.S. ParkS.Y. KimY.M. Anti-angiogenic effects of resveratrol in combination with 5-fluorouracil on B16 murine melanoma cells.Mol. Med. Rep.20151222777278310.3892/mmr.2015.367525936796
    [Google Scholar]
  52. SprouseA.A. HerbertB.S. Resveratrol augments paclitaxel treatment in MDA-MB-231 and paclitaxel-resistant MDA-MB-231 breast cancer cells.Anticancer Res.201434105363537425275030
    [Google Scholar]
  53. FukuiM. YamabeN. ZhuB.T. Resveratrol attenuates the anticancer efficacy of paclitaxel in human breast cancer cells in vitro and in vivo.Eur. J. Cancer201046101882189110.1016/j.ejca.2010.02.00420223651
    [Google Scholar]
  54. BhardwajA. SethiG. Vadhan-RajS. Bueso-RamosC. TakadaY. GaurU. NairA.S. ShishodiaS. AggarwalB.B. Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-κB–regulated antiapoptotic and cell survival gene products in human multiple myeloma cells.Blood200710962293230210.1182/blood‑2006‑02‑00398817164350
    [Google Scholar]
  55. ZhuY. HeW. GaoX. LiB. MeiC. XuR. ChenH. Resveratrol overcomes gefitinib resistance by increasing the intracellular gefitinib concentration and triggering apoptosis, autophagy and senescence in PC9/G NSCLC cells.Sci. Rep.2015511773010.1038/srep1773026635117
    [Google Scholar]
  56. ZhaoY. HuanM. LiuM. ChengY. SunY. CuiH. LiuD. MeiQ. ZhouS. Doxorubicin and resveratrol co-delivery nanoparticle to overcome doxorubicin resistance.Sci. Rep.2016613526710.1038/srep3526727731405
    [Google Scholar]
  57. HarikumarK.B. KunnumakkaraA.B. SethiG. DiagaradjaneP. AnandP. PandeyM.K. GelovaniJ. KrishnanS. GuhaS. AggarwalB.B. Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer.Int. J. Cancer2010127225726810.1002/ijc.2504119908231
    [Google Scholar]
  58. FarrandL. ByunS. KimJ.Y. Im-AramA. LeeJ. LimS. LeeK.W. SuhJ.Y. LeeH.J. TsangB.K. Piceatannol enhances cisplatin sensitivity in ovarian cancer via modulation of p53, X-linked inhibitor of apoptosis protein (XIAP), and mitochondrial fission.J. Biol. Chem.201328833237402375010.1074/jbc.M113.48768623833193
    [Google Scholar]
  59. RaiG. MishraS. SumanS. ShuklaY. Resveratrol improves the anticancer effects of doxorubicin in vitro and in vivo models: A mechanistic insight.Phytomedicine201623323324210.1016/j.phymed.2015.12.02026969377
    [Google Scholar]
  60. Resveratrol in treating patients with colorectal cancer that can be removed by surg.NC Patent T004335762024
  61. A biological study of resveratrol's effects on notch-1 signaling in subjects with low grade gastrointestinal tumors.NC Patent T014765922024
  62. Resveratrol for patients with colon cancer.NC Patent T002563342005
  63. HowellsL.M. BerryD.P. ElliottP.J. JacobsonE.W. HoffmannE. HegartyB. BrownK. StewardW.P. GescherA.J. Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases--safety, pharmacokinetics, and pharmacodynamics.Cancer Prev. Res. (Phila.)2011491419142510.1158/1940‑6207.CAPR‑11‑014821680702
    [Google Scholar]
  64. PopatR. PlesnerT. DaviesF. CookG. CookM. ElliottP. JacobsonE. GumbletonT. OakerveeH. A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma.Br. J. Haematol.2013160571410.1111/bjh.12154.
    [Google Scholar]
  65. WhittleK.J. DunphyP.J. PennockJ.F. The isolation and properties of δ-tocotrienol from Hevea latex.Biochem. J.1966100113814510.1042/bj10001385965249
    [Google Scholar]
  66. AggarwalB.B. SundaramC. PrasadS. KannappanR. Tocotrienols, the vitamin E of the 21st century: Its potential against cancer and other chronic diseases.Biochem. Pharmacol.201080111613163110.1016/j.bcp.2010.07.04320696139
    [Google Scholar]
  67. NesaretnamK. GuthrieN. ChambersA.F. CarrollK.K. Effect of tocotrienols on the growth of a human breast cancer cell line in culture.Lipids199530121139114310.1007/BF025366158614304
    [Google Scholar]
  68. ParkerR.A. PearceB.C. ClarkR.W. GordonD.A. WrightJ.J. Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.J. Biol. Chem.199326815112301123810.1016/S0021‑9258(18)82115‑98388388
    [Google Scholar]
  69. HusainK. Role of tocotrienols in chemosensitization of cancer.Role of Nutraceuticals in Cancer ChemosensitizationAcademic Press2018777910.1016/B978‑0‑12‑812373‑7.00004‑8
    [Google Scholar]
  70. SunW. XuW. LiuH. LiuJ. WangQ. ZhouJ. DongF. ChenB. γ-Tocotrienol induces mitochondria-mediated apoptosis in human gastric adenocarcinoma SGC-7901 cells.J. Nutr. Biochem.200920427628410.1016/j.jnutbio.2008.03.00318602811
    [Google Scholar]
  71. ParkS.K. SandersB.G. KlineK. Tocotrienols induce apoptosis in breast cancer cell lines via an endoplasmic reticulum stress-dependent increase in extrinsic death receptor signaling.Breast Cancer Res. Treat.2010124236137510.1007/s10549‑010‑0786‑220157774
    [Google Scholar]
  72. SrivastavaJ.K. GuptaS. Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells.Biochem. Biophys. Res. Commun.2006346244745310.1016/j.bbrc.2006.05.14716762318
    [Google Scholar]
  73. AgarwalM.K. AgarwalM.L. AtharM. GuptaS. Tocotrienol-rich fraction of palm oil activates p53, modulates Bax/Bcl-2 ratio and induces apoptosis independent of cell cycle association.Cell Cycle20043220019910.4161/cc.3.2.63714712090
    [Google Scholar]
  74. WangC. HusainK. ZhangA. CentenoB.A. ChenD.T. TongZ. SebtiS.M. MalafaM.P. EGR-1/Bax pathway plays a role in vitamin E δ-tocotrienol-induced apoptosis in pancreatic cancer cells.J. Nutr. Biochem.201526879780710.1016/j.jnutbio.2015.02.00825997867
    [Google Scholar]
  75. NesaretnamK. MeganathanP. VeerasenanS.D. SelvadurayK.R. Tocotrienols and breast cancer: The evidence to date.Genes Nutr.2012713910.1007/s12263‑011‑0224‑z21516480
    [Google Scholar]
  76. Tocotrienol in Combination with Neoadjuvant Chemotherapy for Women with Breast Cancer (NeoToc). Available from: https://clinicaltrials.gov/study/NCT02909751 on June 16, 2024).
  77. SpringettG.M. HusainK. NeugerA. CentenoB. ChenD.T. HutchinsonT.Z. LushR.M. SebtiS. MalafaM.P. A phase I safety, pharmacokinetic, and pharmacodynamic presurgical trial of vitamin E δ-tocotrienol in patients with pancreatic ductal neoplasia.EBioMedicine20152121987199510.1016/j.ebiom.2015.11.02526844278
    [Google Scholar]
  78. PrasadS. TyagiA. K. AggarwalB. B. Chemosensitization by ursolic acid: A new avenue for cancer therapyRole of Nutraceuticals in Cancer ChemosensitizationAcademic Press20189910910.1016/B978‑0‑12‑812373‑7.00005‑X
    [Google Scholar]
  79. YadavV.R. PrasadS. SungB. KannappanR. AggarwalB.B. Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer.Toxins20102102428246610.3390/toxins210242822069560
    [Google Scholar]
  80. WuC.C. ChengC.H. LeeY.H. ChangI.L. ChenH.Y. HsiehC.P. ChuehP.J. Ursolic acid triggers apoptosis in human osteosarcoma cells via caspase activation and the ERK1/2 MAPK pathway.J. Agric. Food Chem.201664214220422610.1021/acs.jafc.6b0054227171502
    [Google Scholar]
  81. LinC.C. HuangC.Y. MongM.C. ChanC.Y. YinM.C. Antiangiogenic potential of three triterpenic acids in human liver cancer cells.J. Agric. Food Chem.201159275576210.1021/jf103904b21175131
    [Google Scholar]
  82. WangX.H. ZhouS.Y. QianZ.Z. ZhangH.L. QiuL.H. SongZ. ZhaoJ. WangP. HaoX.S. WangH.Q. Evaluation of toxicity and single-dose pharmacokinetics of intravenous ursolic acid liposomes in healthy adult volunteers and patients with advanced solid tumors.Expert Opin. Drug Metab. Toxicol.20139211712510.1517/17425255.2013.73866723134084
    [Google Scholar]
  83. QianZ. WangX. SongZ. ZhangH. ZhouS. ZhaoJ. WangH. A phase I trial to evaluate the multiple-dose safety and antitumor activity of ursolic acid liposomes in subjects with advanced solid tumors.BioMed Res. Int.201520151710.1155/2015/80971425866811
    [Google Scholar]
  84. SungB. Role of fisetin in chemosensitization.Role of Nutraceuticals in Cancer ChemosensitizationAcademic Press201811113910.1016/B978‑0‑12‑812373‑7.00006‑1
    [Google Scholar]
  85. SuhY. AfaqF. JohnsonJ.J. MukhtarH. A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-κB-signaling pathways.Carcinogenesis200830230030710.1093/carcin/bgn26919037088
    [Google Scholar]
  86. DiehlJ.A. Cycling to cancer with cyclin D1.Cancer Biol. Ther.20021322623110.4161/cbt.7212432268
    [Google Scholar]
  87. LimD.Y. ParkJ.H.Y. Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin.Am. J. Physiol. Gastrointest. Liver Physiol.20092965G1060G106810.1152/ajpgi.90490.200819264955
    [Google Scholar]
  88. SmithM.L. MurphyK. DoucetteC.D. GreenshieldsA.L. HoskinD.W. The dietary flavonoid fisetin causes cell cycle arrest, caspase-dependent apoptosis, and enhanced cytotoxicity of chemotherapeutic drugs in triple-negative breast cancer cells.J. Cell. Biochem.201611781913192510.1002/jcb.2549026755433
    [Google Scholar]
  89. WuM.S. LienG.S. ShenS.C. YangL.Y. ChenY.C. N-acetyl-L-cysteine enhances fisetin-induced cytotoxicity via induction of ROS-independent apoptosis in human colonic cancer cells.Mol. Carcinog.201453S1Suppl. 1E119E12910.1002/mc.2205324019108
    [Google Scholar]
  90. TouilY.S. SeguinJ. SchermanD. ChabotG.G. Improved antiangiogenic and antitumour activity of the combination of the natural flavonoid fisetin and cyclophosphamide in Lewis lung carcinoma-bearing mice.Cancer Chemother. Pharmacol.201168244545510.1007/s00280‑010‑1505‑821069336
    [Google Scholar]
  91. TripathiR. SamadderT. GuptaS. SuroliaA. ShahaC. Anticancer activity of a combination of cisplatin and fisetin in embryonal carcinoma cells and xenograft tumors.Mol. Cancer Ther.201110225526810.1158/1535‑7163.MCT‑10‑060621216935
    [Google Scholar]
  92. PalH.C. BaxterR.D. HuntK.M. AgarwalJ. ElmetsC.A. AtharM. AfaqF. Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells.Oncotarget2015629282962831110.18632/oncotarget.506426299806
    [Google Scholar]
  93. KaleV.P. GilhooleyP.J. PhadtareS. NabavizadehA. PandeyM.K. Role of Gambogic Acid in Chemosensitization of Cancer.Role of Nutraceuticals in Cancer Chemosensitization.Academic Press2018
    [Google Scholar]
  94. PandeyM.K. KareliaD. AminS.G. Gambogic acid and its role in chronic diseases.Anti-inflammatory Nutraceuticals and Chronic DiseasesSpringer201637539510.1007/978‑3‑319‑41334‑1_15
    [Google Scholar]
  95. KashyapD. MondalR. TuliH.S. KumarG. SharmaA.K. Molecular targets of gambogic acid in cancer: Recent trends and advancements.Tumour Biol.20163710129151292510.1007/s13277‑016‑5194‑827448303
    [Google Scholar]
  96. PandeyM.K. SungB. AhnK.S. KunnumakkaraA.B. ChaturvediM.M. AggarwalB.B. Gambogic acid, a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-κB signaling pathway.Blood2007110103517352510.1182/blood‑2007‑03‑07961617673602
    [Google Scholar]
  97. PrasadS. PandeyM.K. YadavV.R. AggarwalB.B. Gambogic acid inhibits STAT3 phosphorylation through activation of protein tyrosine phosphatase SHP-1: Potential role in proliferation and apoptosis.Cancer Prev. Res. (Phila.)2011471084109410.1158/1940‑6207.CAPR‑10‑034021490133
    [Google Scholar]
  98. LiX. LiuS. HuangH. LiuN. ZhaoC. LiaoS. YangC. LiuY. ZhaoC. LiS. LuX. LiuC. GuanL. ZhaoK. ShiX. SongW. ZhouP. DongX. GuoH. WenG. ZhangC. JiangL. MaN. LiB. WangS. TanH. WangX. DouQ.P. LiuJ. Gambogic acid is a tissue-specific proteasome inhibitor in vitro and in vivo.Cell Rep.20133121122210.1016/j.celrep.2012.11.02323260670
    [Google Scholar]
  99. ShiX. ChenX. LiX. LanX. ZhaoC. LiuS. HuangH. LiuN. LiaoS. SongW. ZhouP. WangS. XuL. WangX. DouQ.P. LiuJ. Gambogic acid induces apoptosis in imatinib-resistant chronic myeloid leukemia cells via inducing proteasome inhibition and caspase-dependent Bcr-Abl downregulation.Clin. Cancer Res.201420115116310.1158/1078‑0432.CCR‑13‑106324334603
    [Google Scholar]
  100. ZhaoW. ZhouS-F. ZhangZ-P. XuG-P. LiX-B. YanJ.L. Gambogic acid inhibits the growth of osteosarcoma cells in vitro by inducing apoptosis and cell cycle arrest.Oncol. Rep.20112551289129521331449
    [Google Scholar]
  101. ZhaoW. XiaS.Q. ZhuangJ.P. ZhangZ.P. YouC.C. YanJ.L. XuG.P. Hypoxia-induced resistance to cisplatin-mediated apoptosis in osteosarcoma cells is reversed by gambogic acid independently of HIF-1α.Mol. Cell. Biochem.20164201-21810.1007/s11010‑016‑2759‑127473145
    [Google Scholar]
  102. ZhouZ.T. Phase I human tolerability trail of Gambogic acid.Chin. New Drugs2007163
    [Google Scholar]
  103. ChiY. ZhanX. YuH. XieG. WangZ. XiaoW. WangY. XiongF. HuJ. YangL. CuiC. WangJ. An open-labeled, randomized, multicenter phase IIa study of gambogic acid injection for advanced malignant tumors.Chin. Med. J. (Engl.)201312691642164610.3760/cma.j.issn.0366‑6999.2012258223652044
    [Google Scholar]
  104. ShuklaA. S. JhaA. K. KumariR. RawatK. SyedaS. ShrivastavaA. Role of catechins in chemosensitization.Role of Nutraceuticals in Cancer Chemosensitization.Academic Press2018169198
    [Google Scholar]
  105. HayakawaS. SaitoK. MiyoshiN. OhishiT. OishiY. MiyoshiM. NakamuraY. Anti-cancer effects of green tea by either anti-or pro-oxidative mechanisms.Asian Pac. J. Cancer Prev.20161741649165410.7314/APJCP.2016.17.4.164927221834
    [Google Scholar]
  106. PunathilT. TollefsbolT.O. KatiyarS.K. EGCG inhibits mammary cancer cell migration through inhibition of nitric oxide synthase and guanylate cyclase.Biochem. Biophys. Res. Commun.2008375116216710.1016/j.bbrc.2008.07.15718692479
    [Google Scholar]
  107. SaekiK. KobayashiN. InazawaY. ZhangH. NishitohH. IchijoH. SaekiK. IsemuraM. YuoA. Oxidation-triggered c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways for apoptosis in human leukaemic cells stimulated by epigallocatechin-3-gallate (EGCG): A distinct pathway from those of chemically induced and receptor-mediated apoptosis.Biochem. J.2002368370572010.1042/bj2002010112206715
    [Google Scholar]
  108. HenningS.M. WangP. SaidJ.W. HuangM. GroganT. ElashoffD. CarpenterC.L. HeberD. AronsonW.J. Randomized clinical trial of brewed green and black tea in men with prostate cancer prior to prostatectomy.Prostate201575555055910.1002/pros.2294325545744
    [Google Scholar]
  109. Available from: https://clinicaltrials.gov/study/NCT0051624 on June 11, 2024).
  110. Green Tea and Reduction of Breast Cancer Risk. Available from: https://clinicaltrials.gov/study/NCT00917735 on May 31, 2024).
  111. Green Tea in Breast Cancer Patients. Available from: https://clinicaltrials.gov/study/NCT00949923 on May 24, 2024).
  112. ShimizuM. FukutomiY. NinomiyaM. NaguraK. KatoT. ArakiH. SuganumaM. FujikiH. MoriwakiH. Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study.Cancer Epidemiol. Biomarkers Prev.200817113020302510.1158/1055‑9965.EPI‑08‑052818990744
    [Google Scholar]
  113. Polyphenon E in Treating Patients with High-Risk of Colorectal Cancer. Available from: https://clinicaltrials.gov/study/NCT01606124 on June 3, 2024).
  114. DheerajA. TailorD. SinghS.P. Anticancer attributes of silibinin: Chemo and radiosensitization of cancer.Role of Nutraceuticals in Cancer ChemosensitizationAcademic Press2018199220
    [Google Scholar]
  115. BasiriA. PashaiaslM. The toxic effect of silibinin and paclitaxel combination on endometrial cancer cell line.JAUMS201616323330
    [Google Scholar]
  116. CuyàsE. Pérez-SánchezA. MicolV. MenendezJ.A. Bosch-BarreraJ. STAT3-targeted treatment with silibinin overcomes the acquired resistance to crizotinib in ALK -rearranged lung cancer.Cell Cycle201615243413341810.1080/15384101.2016.124524927753543
    [Google Scholar]
  117. PriegoN. ZhuL. MonteiroC. MuldersM. WasilewskiD. BindemanW. DoglioL. MartínezL. Martínez-SaezE. Ramón y CajalS. MegíasD. Hernández-EncinasE. Blanco-AparicioC. MartínezL. ZarzuelaE. MuñozJ. Fustero-TorreC. Piñeiro-YáñezE. Hernández-LaínA. BerteroL. PoliV. Sanchez-MartinezM. MenendezJ.A. SoffiettiR. Bosch-BarreraJ. ValienteM. STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis.Nat. Med.20182471024103510.1038/s41591‑018‑0044‑429892069
    [Google Scholar]
  118. BhartiA.C. RajanP. JadliM. PandeD. SinghT. Berberine as an adjuvant and sensitizer to current chemotherapy.Role of Nutraceuticals in Cancer Chemosensitization.Academic Press201822124010.1016/B978‑0‑12‑812373‑7.00011‑5
    [Google Scholar]
  119. LinH-L. LiuT-Y. WuC-W. ChiC-W. Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to paclitaxel.Br. J. Cancer199981341642210.1038/sj.bjc.669071010507765
    [Google Scholar]
  120. LeeS-J. NohH-J. SungE-G. SongI-H. KimJ-Y. KwonT.K. LeeT.J. Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated downregulation of c-FLIP and Mcl-1 proteins.Int. J. Oncol.201138248549210.3892/ijo.2010.87821170508
    [Google Scholar]
  121. BaoJ. HuangB. ZouL. ChenS. ZhangC. ZhangY. ChenM. WanJ.B. SuH. WangY. HeC. Hormetic effect of berberine attenuates the anticancer activity of chemotherapeutic agents.PLoS One2015109e013929810.1371/journal.pone.013929826421434
    [Google Scholar]
  122. ZhangC. LiC. ChenS. LiZ. JiaX. WangK. BaoJ. LiangY. WangX. ChenM. LiP. SuH. WanJ.B. LeeS.M.Y. LiuK. HeC. Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AkT/Bcl-2 and Nrf2/HO-1 pathways.Redox Biol.20171111110.1016/j.redox.2016.10.01927835779
    [Google Scholar]
  123. Available from: https://clinicaltrials.gov/search?term=berberine on June 18, 2024).
  124. Study of Berberine Hydrochloride in Prevention of Colorectal Adenomas Recurrence. Available from: https://www.clinicaltrials.gov/study/NCT02226185 on June 22, 2024).
  125. GuptaS.C. Role of Emodin in Chemosensitization of Cancer.Role of Nutraceuticals in Cancer Chemosensitization.Academic Press201824125710.1016/B978‑0‑12‑812373‑7.00012‑7
    [Google Scholar]
  126. MuellerS.O. SchmittM. DekantW. StopperH. SchlatterJ. SchreierP. LutzW.K. Occurrence of emodin, chrysophanol and physcion in vegetables, herbs and liquors. Genotoxicity and anti-genotoxicity of the anthraquinones and of the whole plants.Food Chem. Toxicol.199937548149110.1016/S0278‑6915(99)00027‑710456676
    [Google Scholar]
  127. SuiJ.Q. XieK.P. ZouW. XieM.J. Emodin inhibits breast cancer cell proliferation through the ERα-MAPK/AkT-cyclin D1/Bcl-2 signaling pathway.Asian Pac. J. Cancer Prev.201415156247625110.7314/APJCP.2014.15.15.624725124606
    [Google Scholar]
  128. PrasadS. KimJ.H. GuptaS.C. AggarwalB.B. Targeting death receptors for TRAIL by agents designed by mother nature.Trends Pharmacol. Sci.2014351052053610.1016/j.tips.2014.07.00425128958
    [Google Scholar]
  129. KumarS. BhandariC. SharmaP. Role of piperine in chemoresistance. Role of Nutraceuticals in Cancer Chemosensitization.Academic Press201825928610.1016/B978‑0‑12‑812373‑7.00013‑9
    [Google Scholar]
  130. LaiL. FuQ. LiuY. JiangK. GuoQ. ChenQ. YanB. WangQ. ShenJ. Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1 murine breast cancer model.Acta Pharmacol. Sin.201233452353010.1038/aps.2011.20922388073
    [Google Scholar]
  131. ZhangJ. ZhuX. LiH. LiB. SunL. XieT. ZhuT. ZhouH. YeZ. Piperine inhibits proliferation of human osteosarcoma cells via G2/M phase arrest and metastasis by suppressing MMP-2/-9 expression.Int. Immunopharmacol.2015241505810.1016/j.intimp.2014.11.01225479727
    [Google Scholar]
  132. YaffeP.B. Power CoombsM.R. DoucetteC.D. WalshM. HoskinD.W. Piperine, an alkaloid from black pepper, inhibits growth of human colon cancer cells via G1 arrest and apoptosis triggered by endoplasmic reticulum stress.Mol. Carcinog.201554101070108510.1002/mc.2217624819444
    [Google Scholar]
  133. OuyangD. ZengL. PanH. XuL. WangY. LiuK. HeX. Piperine inhibits the proliferation of human prostate cancer cells via induction of cell cycle arrest and autophagy.Food Chem. Toxicol.20136042443010.1016/j.fct.2013.08.00723939040
    [Google Scholar]
  134. FofariaN.M. KimS.H. SrivastavaS.K. Piperine causes G1 phase cell cycle arrest and apoptosis in melanoma cells through checkpoint kinase-1 activation.PLoS One201495e9429810.1371/journal.pone.009429824804719
    [Google Scholar]
  135. DoucetteC.D. HilchieA.L. LiwskiR. HoskinD.W. Piperine, a dietary phytochemical, inhibits angiogenesis.J. Nutr. Biochem.201324123123910.1016/j.jnutbio.2012.05.00922902327
    [Google Scholar]
  136. AbdelhamedS. YokoyamaS. RefaatA. OguraK. YagitaH. AwaleS. SaikiI. Piperine enhances the efficacy of TRAIL-based therapy for triple-negative breast cancer cells.Anticancer Res.20143441893189924692724
    [Google Scholar]
  137. GreenshieldsA.L. DoucetteC.D. SuttonK.M. MaderaL. AnnanH. YaffeP.B. KnickleA.F. DongZ. HoskinD.W. Piperine inhibits the growth and motility of triple-negative breast cancer cells.Cancer Lett.2015357112914010.1016/j.canlet.2014.11.01725444919
    [Google Scholar]
  138. DoM.T. KimH.G. ChoiJ.H. KhanalT. ParkB.H. TranT.P. JeongT.C. JeongH.G. Antitumor efficacy of piperine in the treatment of human HER2-overexpressing breast cancer cells.Food Chem.201314132591259910.1016/j.foodchem.2013.04.12523870999
    [Google Scholar]
  139. DoucetteC.D. GreenshieldsA.L. LiwskiR.S. HoskinD.W. Piperine blocks interleukin-2-driven cell cycle progression in CTLL-2 T lymphocytes by inhibiting multiple signal transduction pathways.Toxicol. Lett.2015234111210.1016/j.toxlet.2015.01.02025655587
    [Google Scholar]
  140. JagadeeshanS. PrasadM.M. Role of deguelin in chemoresistance.Role of Nutraceuticals in Cancer Chemosensitization.Academic Press2018287296
    [Google Scholar]
  141. ChunK.H. KosmederJ.W.II SunS. PezzutoJ.M. LotanR. HongW.K. LeeH.Y. Effects of deguelin on the phosphatidylinositol 3-kinase/AkT pathway and apoptosis in premalignant human bronchial epithelial cells.J. Natl. Cancer Inst.200395429130210.1093/jnci/95.4.29112591985
    [Google Scholar]
  142. WuW. HaiY. ChenL. LiuR.J. HanY.X. LiW.H. LiS. LinS. WuX.R. Deguelin-induced blockade of PI 3K/protein kinase B/MAP kinase signaling in Zebrafish and breast cancer cell lines is mediated by down-regulation of fibroblast growth factor receptor 4 activity. Pharmacol. Res. Perspect.201642e0021210.1002/prp2.21227069628
    [Google Scholar]
  143. LiR. ChenY. ShuW. ChenZ. KeW. Involvement of SRC-3 in deguelin-induced apoptosis in Jurkat cells.Int. J. Hematol.200989562863510.1007/s12185‑009‑0311‑819365708
    [Google Scholar]
  144. DatN.T. LeeJ.H. LeeK. HongY.S. KimY.H. LeeJ.J. Phenolic constituents of Amorpha fruticosa that inhibit NF-κB activation and related gene expression.J. Nat. Prod.200871101696170010.1021/np800383q18841906
    [Google Scholar]
  145. MehtaR. KattaH. AlimirahF. PatelR. MurilloG. PengX. MuzzioM. MehtaR.G. Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.PLoS One201386e6511310.1371/journal.pone.006511323762292
    [Google Scholar]
  146. SuhY.A. KimJ.H. SungM.A. BooH.J. YunH.J. LeeS.H. LeeH.J. MinH.Y. SuhY.G. KimK.W. LeeH.Y. A novel antitumor activity of deguelin targeting the insulin-like growth factor (IGF) receptor pathway via up-regulation of IGF-binding protein-3 expression in breast cancer.Cancer Lett.2013332110210910.1016/j.canlet.2013.01.02223348700
    [Google Scholar]
  147. GillsJ.J. KosmederJ.II MoonR.C. LantvitD.D. PezzutoJ.M. Effect of deguelin on UVB-induced skin carcinogenesis.J. Chemother.200517329730110.1179/joc.2005.17.3.29716041863
    [Google Scholar]
  148. WooJ.K. ChoiD.S. TranH.T. GilbertB.E. HongW.K. LeeH.Y. Liposomal encapsulation of deguelin: Evidence for enhanced antitumor activity in tobacco carcinogen-induced and oncogenic K-ras-induced lung tumorigenesis.Cancer Prev. Res. (Phila.)20092436136910.1158/1940‑6207.CAPR‑08‑023719336726
    [Google Scholar]
  149. KimW.Y. ChangD.J. HennessyB. KangH.J. YooJ. HanS.H. KimY.S. ParkH.J. GeoS-Y. MillsG. KimK.W. HongW.K. SuhY.G. LeeH.Y. A novel derivative of the natural agent deguelin for cancer chemoprevention and therapy.Cancer Prev. Res. (Phila.)20081757758710.1158/1940‑6207.CAPR‑08‑018419139008
    [Google Scholar]
  150. LeeS.C. MinH.Y. ChoiH. BaeS.Y. ParkK.H. HyunS.Y. LeeH.J. MoonJ. ParkS.H. KimJ.Y. AnH. ParkS.J. SeoJ.H. LeeS. KimY.M. ParkH.J. LeeS.K. LeeJ. LeeJ. KimK.W. SuhY.G. LeeH.Y. Deguelin analogue SH-1242 inhibits Hsp90 activity and exerts potent anticancer efficacy with limited neurotoxicity.Cancer Res.201676368669910.1158/0008‑5472.CAN‑15‑149226645561
    [Google Scholar]
  151. BanerjeeS. ParasramkaM.A. ParuthyS.B. Garcinol: Preclinical perspective underpinning chemo- and radiosensitization of cancer.Role of nutraceuticals in cancer chemosensitization.Elsevier2018297324
    [Google Scholar]
  152. SurhY.J. ChunK.S. ChaH.H. HanS.S. KeumY.S. ParkK.K. LeeS.S. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: Down-regulation of COX-2 and iNOS through suppression of NF-κB activation.Mutat. Res.2001480-48124326810.1016/S0027‑5107(01)00183‑X11506818
    [Google Scholar]
  153. LiaoC.H. SangS. LiangY.C. HoC.T. LinJ.K. Suppression of inducible nitric oxide synthase and cyclooxygenase-2 in downregulating nuclear factor-kappa B pathway by Garcinol.Mol. Carcinog.200441314014910.1002/mc.2005015390082
    [Google Scholar]
  154. YamaguchiF. SaitoM. ArigaT. YoshimuraY. NakazawaH. Free radical scavenging activity and antiulcer activity of garcinol from Garcinia indica fruit rind.J. Agric. Food Chem.20004862320232510.1021/jf990908c10888544
    [Google Scholar]
  155. SaadatN. GuptaS.V. Potential role of garcinol as an anticancer agent.J. Oncol.201220121810.1155/2012/64720622745638
    [Google Scholar]
  156. LiuC. HoP.C.L. WongF.C. SethiG. WangL.Z. GohB.C. Garcinol: Current status of its anti-oxidative, anti-inflammatory and anti-cancer effects.Cancer Lett.2015362181410.1016/j.canlet.2015.03.01925796441
    [Google Scholar]
  157. Kostanová-PoliakováD. SabováL. Anti-apoptotic proteins-targets for chemosensitization of tumor cells and cancer treatment.Neoplasma200552644144916284687
    [Google Scholar]
  158. ChenC.S. LeeC.H. HsiehC.D. HoC.T. PanM.H. HuangC.S. TuS.H. WangY.J. ChenL.C. ChangY.J. WeiP.L. YangY.Y. WuC.H. HoY.S. Nicotine-induced human breast cancer cell proliferation attenuated by garcinol through down-regulation of the nicotinic receptor and cyclin D3 proteins.Breast Cancer Res. Treat.20111251738710.1007/s10549‑010‑0821‑320229177
    [Google Scholar]
  159. YoshidaK. TanakaT. HiroseY. YamaguchiF. KohnoH. ToidaM. HaraA. SugieS. ShibataT. MoriH. Dietary garcinol inhibits 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in rats.Cancer Lett.20052211293910.1016/j.canlet.2004.08.01615797624
    [Google Scholar]
  160. RabikC.A. DolanM.E. Molecular mechanisms of resistance and toxicity associated with platinating agents.Cancer Treat. Rev.200733192310.1016/j.ctrv.2006.09.00617084534
    [Google Scholar]
  161. LiF. ShanmugamM.K. SiveenK.S. WangF. OngT.H. LooS.Y. SwamyM.M.M. MandalS. KumarA.P. GohB.C. KunduT. AhnK.S. WangL.Z. HuiK.M. SethiG. Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers.Oncotarget2015675147516310.18632/oncotarget.288125762616
    [Google Scholar]
  162. ShibataM.A. IinumaM. MorimotoJ. KuroseH. AkamatsuK. OkunoY. AkaoY. OtsukiY. α-Mangostin extracted from the pericarp of the mangosteen (Garcinia mangostanaLinn) reduces tumor growth and lymph node metastasis in an immunocompetent xenograft model of metastatic mammary cancer carrying a p53 mutation.BMC Med.2011916910.1186/1741‑7015‑9‑6921639868
    [Google Scholar]
  163. SpiraA. EttingerD.S. Multidisciplinary management of lung cancer.N. Engl. J. Med.2004350437939210.1056/NEJMra03553614736930
    [Google Scholar]
  164. OhnishiH. AsamotoM. TujimuraK. HokaiwadoN. TakahashiS. OgawaK. KuribayashiM. OgisoT. OkuyamaH. ShiraiT. Inhibition of cell proliferation by nobiletin, a dietary phytochemical, associated with apoptosis and characteristic gene expression, but lack of effect on early rat hepatocarcinogenesis in vivo.Cancer Sci.2004951293694210.1111/j.1349‑7006.2004.tb03180.x15596041
    [Google Scholar]
  165. EinbondL. MightyJ. KashiwazakiR. FigueroaM. JaleesF. AcunaU. LeGendreO. FosterD. KennellyE. E. Garcinia benzophenones inhibit the growth of human colon cancer cells and synergize with sulindac sulfide and turmeric.Anticancer. Agents Med. Chem.201313101540155010.2174/18715206113139990095
    [Google Scholar]
  166. CheckerR. PatwardhanR.S. SharmaD. Chemopreventive and anticancer effects of plumbagin: Novel mechanism(s) via modulation of cellular redox.Role of Nutraceuticals in Cancer ChemosensitizationAcademic Press2018325321
    [Google Scholar]
  167. SandurS.K. IchikawaH. SethiG. AhnK.S. AggarwalB.B. Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) suppresses NF-kappaB activation and NF-kappaB-regulated gene products through modulation of p65 and IkappaBalpha kinase activation, leading to potentiation of apoptosis induced by cytokine and chemotherapeutic agents.J. Biol. Chem.200628125170231703310.1074/jbc.M60159520016624823
    [Google Scholar]
  168. ZhaoY-L. LuD.P. Effects of plumbagin on the human acute promyelocytic leukemia cells in vitro.J. Exp. Hematol200614220821116638181
    [Google Scholar]
  169. HsuY.L. ChoC.Y. KuoP.L. HuangY.T. LinC.C. Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) induces apoptosis and cell cycle arrest in A549 cells through p53 accumulation via c-Jun NH2-terminal kinase-mediated phosphorylation at serine 15 in vitro and in vivo.J. Pharmacol. Exp. Ther.2006318248449410.1124/jpet.105.09886316632641
    [Google Scholar]
  170. LiY.C. HeS.M. HeZ.X. LiM. YangY. PangJ.X. ZhangX. ChowK. ZhouQ. DuanW. ZhouZ.W. YangT. HuangG.H. LiuA. QiuJ.X. LiuJ.P. ZhouS.F. Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/AkT/mTOR pathway in human non-small cell lung cancer cells.Cancer Lett.2014344223925910.1016/j.canlet.2013.11.00124280585
    [Google Scholar]
  171. XuT.P. ShenH. LiuL.X. ShuY.Q. Plumbagin from Plumbago Zeylanica L induces apoptosis in human non-small cell lung cancer cell lines through NF- κB inactivation.Asian Pac. J. Cancer Prev.20131442325233110.7314/APJCP.2013.14.4.232523725135
    [Google Scholar]
  172. KuoP.L. HsuY.L. ChoC.Y. Plumbagin induces G2-M arrest and autophagy by inhibiting the AkT/mammalian target of rapamycin pathway in breast cancer cells.Mol. Cancer Ther.20065123209322110.1158/1535‑7163.MCT‑06‑047817172425
    [Google Scholar]
  173. AhmadA. BanerjeeS. WangZ. KongD. SarkarF.H. Plumbagin-induced apoptosis of human breast cancer cells is mediated by inactivation of NF-κB and Bcl-2.J. Cell. Biochem.200810561461147110.1002/jcb.2196618980240
    [Google Scholar]
  174. YanW. TuB. LiuY. WangT. QiaoH. ZhaiZ. LiH. TangT. Suppressive effects of plumbagin on invasion and migration of breast cancer cells via the inhibition of STAT3 signaling and down-regulation of inflammatory cytokine expressions.Bone Res.20131436237010.4248/BR20130400726273514
    [Google Scholar]
  175. AzizM.H. DreckschmidtN.E. VermaA.K. Plumbagin, a medicinal plant-derived naphthoquinone, is a novel inhibitor of the growth and invasion of hormone-refractory prostate cancer.Cancer Res.200868219024903210.1158/0008‑5472.CAN‑08‑249418974148
    [Google Scholar]
  176. SubramaniyaB.R. SrinivasanG. Mohammed SadullahS.S. DavisN. Baddi Reddi SubhadaraL. HalagowderD. SivasitambaramN.D. Apoptosis inducing effect of plumbagin on colonic cancer cells depends on expression of COX-2.PLoS One201164e1869510.1371/journal.pone.001869521559086
    [Google Scholar]
  177. WangC.C.C. ChiangY.M. SungS.C. HsuY.L. ChangJ.K. KuoP.L. Plumbagin induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human melanoma A375.S2 cells.Cancer Lett.20082591829810.1016/j.canlet.2007.10.00518023967
    [Google Scholar]
  178. KlausV. HartmannT. GambiniJ. GrafP. StahlW. HartwigA. KlotzL.O. 1,4-Naphthoquinones as inducers of oxidative damage and stress signaling in HaCaT human keratinocytes.Arch. Biochem. Biophys.201049629310010.1016/j.abb.2010.02.00220153715
    [Google Scholar]
  179. SandurS.K. PandeyM.K. SungB. AggarwalB.B. 5-hydroxy-2-methyl-1,4-naphthoquinone, a vitamin K3 analogue, suppresses STAT3 activation pathway through induction of protein tyrosine phosphatase, SHP-1: Potential role in chemosensitization.Mol. Cancer Res.20108110711810.1158/1541‑7786.MCR‑09‑025720068065
    [Google Scholar]
  180. ChakrabortyA. Role of zerumbone in the chemosensitization of cancer cells.Role of Nutraceuticals in Cancer Chemosensitization.Academic Press201834334910.1016/B978‑0‑12‑812373‑7.00017‑6
    [Google Scholar]
  181. KitayamaT. YamamotoK. UtsumiR. TakataniM. HillR.K. KawaiY. SawadaS. OkamotoT. Chemistry of zerumbone. 2. Regulation of ring bond cleavage and unique antibacterial activities of zerumbone derivatives.Biosci. Biotechnol. Biochem.200165102193219910.1271/bbb.65.219311758909
    [Google Scholar]
  182. ShanmugamM.K. RajendranP. LiF. KimC. SikkaS. SiveenK.S. KumarA.P. AhnK.S. SethiG. Abrogation of STAT3 signaling cascade by zerumbone inhibits proliferation and induces apoptosis in renal cell carcinoma xenograft mouse model.Mol. Carcinog.2015541097198510.1002/mc.2216624797723
    [Google Scholar]
  183. JorvigJ.E. ChakrabortyA. Zerumbone inhibits growth of hormone refractory prostate cancer cells by inhibiting JAK2/STAT3 pathway and increases paclitaxel sensitivity.Anticancer Drugs201526216016610.1097/CAD.000000000000017125243457
    [Google Scholar]
  184. AbdelwahabS.I. AbdulA.B. ZainZ.N.M. HadiA.H.A. Zerumbone inhibits interleukin-6 and induces apoptosis and cell cycle arrest in ovarian and cervical cancer cells.Int. Immunopharmacol.201212459460210.1016/j.intimp.2012.01.01422330084
    [Google Scholar]
  185. AbdulA.B. AbdelwahabS.I. JalinasJ.B. BiomedB. Al-ZubairiA.S. TahaM.M.E. Combination of zerumbone and cisplatin to treat cervical intraepithelial neoplasia in female BALB/c mice.Int. J. Gynecol. Cancer20091961004101010.1111/IGC.0b013e3181a83b5119820360
    [Google Scholar]
  186. HuZ. ZengQ. ZhangB. LiuH. WangW. Promotion of p53 expression and reactive oxidative stress production is involved in zerumbone-induced cisplatin sensitization of non-small cell lung cancer cells.Biochimie2014107Pt B25726210.1016/j.biochi.2014.09.00125220870
    [Google Scholar]
  187. GirisaS. ShabnamB. MonishaJ. FanL. HalimC.E. ArfusoF. AhnK.S. SethiG. KunnumakkaraA.B. Potential of zerumbone as an anti-cancer agent.Molecules201924473410.3390/molecules2404073430781671
    [Google Scholar]
  188. SaxenaR. Multitalented ginger and its clinical development for cancer treatment.Role of Nutraceuticals in Cancer ChemosensitizationAcademic Press201835137010.1016/B978‑0‑12‑812373‑7.00018‑8
    [Google Scholar]
  189. BaligaM.S. HaniadkaR. PereiraM.M. D’SouzaJ.J. PallatyP.L. BhatH.P. PopuriS. Update on the chemopreventive effects of ginger and its phytochemicals.Crit. Rev. Food Sci. Nutr.201151649952310.1080/1040839100369866921929329
    [Google Scholar]
  190. HaniadkaR. SaldanhaE. SunitaV. PalattyP.L. FayadR. BaligaM.S. A review of the gastroprotective effects of ginger (Zingiber officinale Roscoe). Food Funct.20134684585510.1039/c3fo30337c23612703
    [Google Scholar]
  191. GovindarajanV.S. Ginger-chemistry, technology, and quality evaluation: part 1.Crit. Rev. Food Sci. Nutr.19821711967049579
    [Google Scholar]
  192. GovindarajanV.S. ConnellD.W. Ginger: Chemistry, technology, and quality evaluation: Part 2.CRC Crit. Rev. Food Sci. Nutr.198317318925810.1080/104083982095273486756789
    [Google Scholar]
  193. PeterK.V. Handbook of Herbs and Spices.Woodhead Publishing Series2004
    [Google Scholar]
  194. GrzannaR. LindmarkL. FrondozaC.G. Ginger-An herbal medicinal product with broad anti-inflammatory actions.J. Med. Food20058212513210.1089/jmf.2005.8.12516117603
    [Google Scholar]
  195. RahmaniA.H. ShabrmiF.M. AlyS.M. Active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities.Int. J. Physiol. Pathophysiol. Pharmacol.20146212513625057339
    [Google Scholar]
  196. FlynnD.L. RaffertyM.F. BoctorA.M. Inhibition of human neutrophil 5-lipoxygenase activity by gingerdione, shogaol, capsaicin and related pungent compounds.Prostaglandins Leukot. Med.1986242-319519810.1016/0262‑1746(86)90126‑53467378
    [Google Scholar]
  197. TjendraputraE. TranV.H. Liu-BrennanD. RoufogalisB.D. DukeC.C. Effect of ginger constituents and synthetic analogues on cyclooxygenase-2 enzyme in intact cells.Bioorg. Chem.200129315616310.1006/bioo.2001.120811437391
    [Google Scholar]
  198. KimJ.S. LeeS.I. ParkH.W. YangJ.H. ShinT.Y. KimY.C. BaekN.I. KimS.H. ChoiS.U. KwonB.M. LeemK.H. JungM.Y. KimD.K. Cytotoxic components from the dried rhizomes of Zingiber officinale Roscoe.Arch. Pharm. Res.200831441541810.1007/s12272‑001‑1172‑y18449496
    [Google Scholar]
  199. 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.2009.05.01219481070
    [Google Scholar]
  200. ParkY.J. WenJ. BangS. ParkS.W. SongS.Y. [6]-Gingerol induces cell cycle arrest and cell death of mutant p53-expressing pancreatic cancer cells.Yonsei Med. J.200647568869710.3349/ymj.2006.47.5.68817066513
    [Google Scholar]
  201. YangG. ZhongL. JiangL. GengC. CaoJ. SunX. MaY. Genotoxic effect of 6-gingerol on human hepatoma G2 cells.Chem. Biol. Interact.20101851121710.1016/j.cbi.2010.02.01720167213
    [Google Scholar]
  202. ChenC.Y. YangY.H. KuoS.Y. Effect of [6]-shogaol on cytosolic Ca2+ levels and proliferation in human oral cancer cells (OC2).J. Nat. Prod.20107381370137410.1021/np100213a20669930
    [Google Scholar]
  203. GanF.F. NagleA.A. AngX. HoO.H. TanS.H. YangH. ChuiW.K. ChewE.H. Shogaols at proapoptotic concentrations induce G2/M arrest and aberrant mitotic cell death associated with tubulin aggregation.Apoptosis201116885686710.1007/s10495‑011‑0611‑321598039
    [Google Scholar]
  204. HungJ.Y. HsuY.L. LiC.T. KoY.C. NiW.C. HuangM.S. KuoP.L. 6-Shogaol, an active constituent of dietary ginger, induces autophagy by inhibiting the AkT/mTOR pathway in human non-small cell lung cancer A549 cells.J. Agric. Food Chem.200957209809981610.1021/jf902315e19799425
    [Google Scholar]
  205. PanM.H. HsiehM.C. KuoJ.M. LaiC.S. WuH. SangS. HoC.T. 6-Shogaol induces apoptosis in human colorectal carcinoma cells via ROS production, caspase activation, and GADD 153 expression.Mol. Nutr. Food Res.200852552753710.1002/mnfr.20070015718384088
    [Google Scholar]
  206. RadhakrishnanE.K. BavaS.V. NarayananS.S. NathL.R. ThulasidasanA.K.T. SoniyaE.V. AntoR.J. [6]-Gingerol induces caspase-dependent apoptosis and prevents PMA-induced proliferation in colon cancer cells by inhibiting MAPK/AP-1 signaling.PLoS One201498e10440110.1371/journal.pone.010440125157570
    [Google Scholar]
  207. SahaA. BlandoJ. SilverE. BeltranL. SesslerJ. DiGiovanniJ. 6-Shogaol from dried ginger inhibits growth of prostate cancer cells both in vitro and in vivo through inhibition of STAT3 and NF-κB signaling.Cancer Prev. Res. (Phila.)20147662763810.1158/1940‑6207.CAPR‑13‑042024691500
    [Google Scholar]
  208. HsuY.L. ChenC.Y. HouM.F. TsaiE.M. JongY.J. HungC.H. KuoP.L. 6-Dehydrogingerdione, an active constituent of dietary ginger, induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human breast cancer cells.Mol. Nutr. Food Res.20105491307131710.1002/mnfr.20090012520175081
    [Google Scholar]
  209. Di FioreF. Van CutsemE. Acute and long-term gastrointestinal consequences of chemotherapy.Best Pract. Res. Clin. Gastroenterol.200923111312410.1016/j.bpg.2008.11.01619258191
    [Google Scholar]
  210. HerrstedtJ. DombernowskyP. Anti-emetic therapy in cancer chemotherapy: Current status.Basic Clin. Pharmacol. Toxicol.2007101314315010.1111/j.1742‑7843.2007.00122.x17697032
    [Google Scholar]
  211. MinamiM. EndoT. HirafujiM. HamaueN. LiuY. HiroshigeT. NemotoM. SaitoH. YoshiokaM. Pharmacological aspects of anticancer drug-induced emesis with emphasis on serotonin release and vagal nerve activity.Pharmacol. Ther.200399214916510.1016/S0163‑7258(03)00057‑312888110
    [Google Scholar]
  212. MarxW. RiedK. McCarthyA.L. VitettaL. SaliA. McKavanaghD. IsenringL. Ginger—Mechanism of action in chemotherapy-induced nausea and vomiting: A review.Crit. Rev. Food Sci. Nutr.201757114114610.1080/10408398.2013.86559025848702
    [Google Scholar]
  213. Abdel-AzizH. WindeckT. PlochM. VerspohlE.J. Mode of action of gingerols and shogaols on 5-HT3 receptors: Binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum.Eur. J. Pharmacol.20065301-213614310.1016/j.ejphar.2005.10.04916364290
    [Google Scholar]
  214. HuangQ. IwamotoM. AokiS. TanakaN. TajimaK. YamaharaJ. TakaishiY. YoshidaM. TomimatsuT. TamaiY. Anti-5-hydroxytryptamine3 effect of galanolactone, diterpenoid isolated from ginger.Chem. Pharm. Bull. (Tokyo)199139239739910.1248/cpb.39.3972054863
    [Google Scholar]
  215. PanahiY. SaadatA. SahebkarA. HashemianF. TaghikhaniM. AbolhasaniE. Effect of ginger on acute and delayed chemotherapy-induced nausea and vomiting: A pilot, randomized, open-label clinical trial.Integr. Cancer Ther.201211320421110.1177/153473541143320122313739
    [Google Scholar]
  216. PillaiA.K. SharmaK.K. GuptaY.K. BakhshiS. Anti-emetic effect of ginger powder versus placebo as an add-on therapy in children and young adults receiving high emetogenic chemotherapy.Pediatr. Blood Cancer201156223423810.1002/pbc.2277820842754
    [Google Scholar]
  217. RyanJ.L. HecklerC.E. RoscoeJ.A. DakhilS.R. KirshnerJ. FlynnP.J. HickokJ.T. MorrowG.R. Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: A URCC CCOP study of 576 patients.Support. Care Cancer20122071479148910.1007/s00520‑011‑1236‑321818642
    [Google Scholar]
  218. ZickS.M. RuffinM.T. LeeJ. NormolleD.P. SidenR. AlrawiS. BrennerD.E. Phase II trial of encapsulated ginger as a treatment for chemotherapy-induced nausea and vomiting.Support. Care Cancer200917556357210.1007/s00520‑008‑0528‑819005687
    [Google Scholar]
  219. MarxW. McCarthyA.L. RiedK. VitettaL. McKavanaghD. ThomsonD. SaliA. IsenringL. Can ginger ameliorate chemotherapy-induced nausea? Protocol of a randomized double blind, placebo-controlled trial.BMC Complement. Altern. Med.201414113410.1186/1472‑6882‑14‑13424712653
    [Google Scholar]
  220. KarnaP. ChaganiS. GundalaS.R. RidaP.C.G. AsifG. SharmaV. GuptaM.V. AnejaR. Benefits of whole ginger extract in prostate cancer.Br. J. Nutr.2012107447348410.1017/S000711451100330821849094
    [Google Scholar]
  221. Dai, H.; Fan, Q.; Wang, C. Recent applications of immunomodulatory biomaterials for disease immunotherapy.Exploration2022220210157
    [Google Scholar]
  222. Feng, Y.; Zhang, Z.; Tang, W.; Dai, Y. Gel/hydrogel-based in situ biomaterial platforms for cancer postoperative treatment and recovery.Exploration2023320220173
    [Google Scholar]
  223. ZhangS. LiD. LiuY. QinC. TongL. XuL. Multifunctional exosome-driven pancreatic cancer diagnostics and therapeutics.Extracellular Vesicle2023210002210.1016/j.vesic.2023.100022
    [Google Scholar]
  224. ZhaoJ. XuL. YangD. TangH. ChenY. ZhangX. XuY. OuR. LiD. Exosome-driven liquid biopsy for breast cancer: Recent advances in isolation, biomarker identification and detection.Extracellular Vesicle2022110000610.1016/j.vesic.2022.100006
    [Google Scholar]
  225. Di ChioC. PrevitiS. De LucaF. AllegraA. ZappalàM. EttariR. Drug combination studies of PS-1 and quercetin against rhodesain of Trypanosoma brucei.Nat. Prod. Res.202236164282428610.1080/14786419.2021.197899334533390
    [Google Scholar]
  226. Di ChioC. PrevitiS. De LucaF. BogaczM. ZimmerC. WagnerA. SchirmeisterT. ZappalàM. EttariR. Drug combination studies of the dipeptide nitrile CD24 with curcumin: A new strategy to synergistically inhibit rhodesain of Trypanosoma brucei rhodesiense.Int. J. Mol. Sci.202223221447010.3390/ijms23221447036430948
    [Google Scholar]
  227. Di ChioC. PrevitiS. StarvaggiJ. De LucaF. CalabròM.L. ZappalàM. EttariR. Drug combination studies of isoquinolinone AM12 with curcumin or quercetin: A new combination strategy to synergistically inhibit 20S proteasome.Int. J. Mol. Sci.202425191070810.3390/ijms25191070839409037
    [Google Scholar]
  228. Di ChioC. PrevitiS. TotaroN. De LucaF. AllegraA. SchirmeisterT. ZappalàM. EttariR. Dipeptide nitrile CD34 with curcumin: A new improved combination strategy to synergistically inhibit rhodesain of Trypanosoma brucei rhodesiense.Int. J. Mol. Sci.20232410847710.3390/ijms2410847737239824
    [Google Scholar]
  229. EttariR. PrevitiS. Di ChioC. MaioranaS. AllegraA. SchirmeisterT. ZappalàM. Drug synergism: Studies of combination of RK-52 and curcumin against rhodesain of Trypanosoma brucei rhodesiense.ACS Med. Chem. Lett.202011580681010.1021/acsmedchemlett.9b0063532435388
    [Google Scholar]
  230. EttariR. PrevitiS. MaioranaS. AllegraA. SchirmeisterT. GrassoS. ZappalàM. Drug combination studies of curcumin and genistein against rhodesain of Trypanosoma brucei.Nat. Prod. Res.201933243577358110.1080/14786419.2018.148392729897253
    [Google Scholar]
  231. Davatgaran-TaghipourY. MasoomzadehS. FarzaeiM.H. BahramsoltaniR. Karimi-SourehZ. RahimiR. AbdollahiM. Polyphenol nanoformulations for cancer therapy: Experimental evidence and clinical perspective.Int. J. Nanomedicine2017122689270210.2147/IJN.S13197328435252
    [Google Scholar]
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