Natural compounds to overcome cancer chemoresistance: Toxicological and clinical issues

Expert Opinion on Drug Metabolism and Toxicology

Volumn 10, Issue 12, 2014, Pages 1677-1690

  Turrini, Eleonora ^a   Ferruzzi, Lorenzo ^a   Fimognari, Carmela ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

5 fluorouracil; Apoptosis; Chemosensitization; Curcumin; Genotoxicity; Oncology; Platinum derivatives; Sulforaphane

Indexed keywords

CURCUMIN; FLUOROURACIL; NATURAL PRODUCT; PLATINUM DERIVATIVE; SULFORAPHANE; ANTINEOPLASTIC AGENT; ISOTHIOCYANIC ACID DERIVATIVE; SULFORAFAN;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER CHEMOTHERAPY; CANCER PATIENT; CANCER RESISTANCE; CANCER STAGING; CANCER SURVIVAL; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; EARLY CANCER; HUMAN; NONHUMAN; REVIEW; ANIMAL; DRUG EFFECTS; DRUG RESISTANCE; NEOPLASMS; PATHOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; CURCUMIN; DRUG RESISTANCE, NEOPLASM; FLUOROURACIL; HUMANS; ISOTHIOCYANATES; NEOPLASMS; PLATINUM COMPOUNDS; SIGNAL TRANSDUCTION;

EID: 84911437697     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2014.972933     Document Type: Review

References (120)

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74
2. Ocker M, Hopfner M. Apoptosis-modulating drugs for improved cancer therapy. Eur Surg Res 2012;48:111-20
3. Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 2003;3:330-8
4. Prestayko AW, D'Aoust JC, Issell BF, Crooke ST. Cisplatin (cisdiamminedichloroplatinum II). Cancer Treat Rev 1979;6:17-39
5. Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 2003;22:7265-79
6. Bowden NA. Nucleotide excision repair: why is it not used to predict response to platinum-based chemotherapy?. Cancer Lett 2014;346:163-71
7. Ammon HP, Wahl MA. Pharmacology of Curcuma longa. Planta Med 1991;57:1-7
8. Chauhan DP. Chemotherapeutic potential of curcumin for colorectal cancer. Curr Pharm Des 2002;8:1695-706
9. Rao CV, Rivenson A, Simi B, Reddy BS. Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res 1995;55:259-66
10. Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer 2005;41:1955-68
11. Shehzad A, Lee YS. Molecular mechanisms of curcumin action: signal transduction. Biofactors 2013;39:27-36
12. Vinod BS, Antony J, Nair HH, et al. Mechanistic evaluation of the signaling events regulating curcumin-mediated chemosensitization of breast cancer cells to 5-fluorouracil. Cell Death Dis 2013;4:e505
13. Eastman A, Schulte N. Enhanced DNA repair as a mechanism of resistance to cis-diamminedichloroplatinum(II). Biochemistry 1988;27:4730-4
14. Li L, Braiteh FS, Kurzrock R. Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis. Cancer 2005;104:1322-31
15. Zhang N, Yin Y, Xu SJ, Chen WS. 5-Fluorouracil: mechanisms of resistance and reversal strategies. Molecules 2008;13:1551-69
16. Raymond E, Faivre S, Chaney S, et al. Cellular and molecular pharmacology of oxaliplatin. Mol Cancer Ther 2002;1:227-35
17. Maccio A, Madeddu C. Cisplatin: an old drug with a newfound efficacy -from mechanisms of action to cytotoxicity. Expert Opin Pharmacother 2013;14:1839-57
18. Wong JY, Huggins GS, Debidda M, et al. Dichloroacetate induces apoptosis in endometrial cancer cells. Gynecol Oncol 2008;109:394-402
19. Demaria M, Giorgi C, Lebiedzinska M, et al. A STAT3-mediated metabolic switch is involved in tumour transformation and STAT3 addiction. Aging (Albany NY) 2010;2:823-42
20. Elstrom RL, Bauer DE, Buzzai M, et al. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 2004;64:3892-9
21. Gough DJ, Corlett A, Schlessinger K, et al. Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 2009;324:1713-16
22. Han Z, Feng J, Hong Z, et al. Silencing of the STAT3 signaling pathway reverses the inherent and induced chemoresistance of human ovarian cancer cells. Biochem Biophys Res Commun 2013;435:188-94
23. Srivastava AN, Gupta A, Srivastava S, et al. Cisplatin combination chemotherapy induces oxidative stress in advance non small cell lung cancer patients. Asian Pac J Cancer Prev 2010;11:465-71
24. Masuda H, Tanaka T, Tateishi M, et al. Detection and cytotoxicity of cisplatininduced superoxide anion in monolayer cultures of a human ovarian cancer cell line. Cancer Chemother Pharmacol 2001;47:155-60
25. Martins NM, Santos NA, Curti C, et al. Cisplatin induces mitochondrial oxidative stress with resultant energetic metabolism impairment, membrane rigidification and apoptosis in rat liver. J Appl Toxicol 2008;28:337-44
26. Spitz DR, Phillips JW, Adams DT, et al. Cellular resistance to oxidative stress is accompanied by resistance to cisplatin: the significance of increased catalase activity and total glutathione in hydrogen peroxide-resistant fibroblasts. J Cell Physiol 1993;156:72-9
27. Chu E, Koeller DM, Johnston PG, et al. Regulation of thymidylate synthase in human colon cancer cells treated with 5-fluorouracil and interferon-gamma. Mol Pharmacol 1993;43:527-33
28. Wang S, Kotamraju S, Konorev E, et al. Activation of nuclear factor-kappaB during doxorubicin-induced apoptosis in endothelial cells and myocytes is proapoptotic: the role of hydrogen peroxide. Biochem J 2002;367:729-40
29. Kodach LL, Bos CL, Duran N, et al. Violacein synergistically increases 5-fluorouracil cytotoxicity, induces apoptosis and inhibits Akt-mediated signal transduction in human colorectal cancer cells. Carcinogenesis 2006;27:508-16
30. Jin W, Wu L, Liang K, et al. Roles of the PI-3K and MEK pathways in Rasmediated chemoresistance in breast cancer cells. Br J Cancer 2003;89:185-91
31. Shehzad A, Wahid F, Lee YS. Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch Pharm (Weinheim) 2010;343:489-99
32. Verschoyle RD, Steward WP, Gescher AJ. Putative cancer chemopreventive agents of dietary originhow safe are they?. Nutr Cancer 2007;59:152-62
33. Akhdar H, Loyer P, Rauch C, et al. Involvement of Nrf2 activation in resistance to 5-fluorouracil in human colon cancer HT-29 cells. Eur J Cancer 2009;45:2219-27
34. Fu Y, Yang G, Zhu F, et al. Antioxidants decrease the apoptotic effect of 5-Fu in colon cancer by regulating Src-dependent caspase-7 phosphorylation. Cell Death Dis 2014;5:e983
35. Li J, Shen F, Guan C, et al. Activation of Nrf2 Protects against Triptolide-Induced Hepatotoxicity. PLoS One 2014;9:e100685
36. Hayes JD, McMahon M. NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem Sci 2009;34:176-88
37. Roos WP, Kaina B. DNA damageinduced cell death: from specific DNA lesions to the DNA damage response and apoptosis. Cancer Lett 2013;332:237-48
38. Yeh PY, Chuang SE, Yeh KH, et al. Increase of the resistance of human cervical carcinoma cells to cisplatin by inhibition of the MEK to ERK signaling pathway partly via enhancement of anticancer drug-induced NF kappa B activation. Biochem Pharmacol 2002;63:1423-30
39. Liang XJ, Finkel T, Shen DW, et al. SIRT1 contributes in part to cisplatin resistance in cancer cells by altering mitochondrial metabolism. Mol Cancer Res 2008;6:1499-506
40. Pectasides D, Fountzilas G, Aravantinos G, et al. Advanced stage mucinous epithelial ovarian cancer: the Hellenic Cooperative Oncology Group experience. Gynecol Oncol 2005;97:436-41
41. Oh WK, Tay MH, Huang J. Is there a role for platinum chemotherapy in the treatment of patients with hormonerefractory prostate cancer?. Cancer 2007;109:477-86
42. Fazio N, Spada F, Giovannini M. Chemotherapy in gastroenteropancreatic (GEP) neuroendocrine carcinomas (NEC): a critical view. Cancer Treat Rev 2013;39:270-4
43. Egawa-Takata T, Endo H, Fujita M, et al. Early reduction of glucose uptake after cisplatin treatment is a marker of cisplatin sensitivity in ovarian cancer. Cancer Sci 2010;101:2171-8
44. Shulga N, Wilson-Smith R, Pastorino JG. Hexokinase II detachment from the mitochondria potentiates cisplatin induced cytotoxicity through a caspase-2 dependent mechanism. Cell Cycle 2009;8:3355-64
45. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as Curecumin: from kitchen to clinic. Biochem Pharmacol 2008;75:787-809
46. Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem 1995;270:24995-5000
47. Li L, Aggarwal BB, Shishodia S, et al. Nuclear factor-kappaB and IkappaB kinase are constitutively active in human pancreatic cells, and their downregulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis. Cancer 2004;101:2351-62
48. Zheng M, Ekmekcioglu S, Walch ET, et al. Inhibition of nuclear factor-kappaB and nitric oxide by curcumin induces G2/M cell cycle arrest and apoptosis in human melanoma cells. Melanoma Res 2004;14:165-71
49. Jobin C, Bradham CA, Russo MP, et al. Curcumin blocks cytokine-mediated NFkappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. J Immunol 1999;163:3474-83
50. Lev-Ari S, Starr A, Vexler A, et al. Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity. Anticancer Res 2006;26:4423-30
51. Dang TP. Notch, apoptosis and cancer. Adv Exp Med Biol 2012;727:199-209
52. Gupta SC, Patchva S, Koh W, Aggarwal BB. Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clin Exp Pharmacol Physiol 2012;39:283-99
53. Perez-Tenorio G, Stal O. Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br J Cancer 2002;86:540-5
54. Hartojo W, Silvers AL, Thomas DG, et al. Curcumin promotes apoptosis, increases chemosensitivity, and inhibits nuclear factor kappaB in esophageal adenocarcinoma. Transl Oncol 2010;3:99-108
55. Patel BB, Sengupta R, Qazi S, et al. 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 Cancer 2008;122:267-73
56. Shakibaei M, Mobasheri A, Lueders C, et al. Curcumin enhances the effect of chemotherapy against colorectal cancer cells by inhibition of NF-kappaB and Src protein kinase signaling pathways. PLoS One 2013;8:e57218
57. Shakibaei M, Buhrmann C, Kraehe P, et al. Curcumin chemosensitizes 5-fluorouracil resistant MMR-deficient human colon cancer cells in high density cultures. PLoS One 2014;9:e85397
58. Kunnumakkara AB, Diagaradjane P, Anand P, et al. Curcumin sensitizes human colorectal cancer to capecitabine by modulation of cyclin D1, COX-2, MMP-9, VEGF and CXCR4 expression in an orthotopic mouse model. Int J Cancer 2009;125:2187-97
59. Chen Y, Liu WH, Chen BL, et al. Plant polyphenol curcumin significantly affects CYP1A2 and CYP2A6 activity in healthy, male Chinese volunteers. Ann Pharmacother 2010;44:1038-45
60. Mulik RS, Monkkonen J, Juvonen RO, et al. Transferrin mediated solid lipid nanoparticles containing curcumin: enhanced in vitro anticancer activity by induction of apoptosis. Int J Pharm 2010;398:190-203
61. Balasubramanian S, Girija AR, Nagaoka Y, et al. Curcumin and 5-fluorouracil-loaded, folate-and transferrin-decorated polymeric magnetic nanoformulation: a synergistic cancer therapeutic approach, accelerated by magnetic hyperthermia. Int J Nanomedicine 2014;9:437-59
62. Montopoli M, Ragazzi E, Froldi G, Caparrotta L. Cell-cycle inhibition and apoptosis induced by curcumin and cisplatin or oxaliplatin in human ovarian carcinoma cells. Cell Prolif 2009;42:195-206
63. Yunos NM, Beale P, Yu JQ, Huq F. Synergism from sequenced combinations of curcumin and epigallocatechin-3-gallate with cisplatin in the killing of human ovarian cancer cells. Anticancer Res 2011;31:1131-40
64. Siomek A, Tujakowski J, Gackowski D, et al. Severe oxidatively damaged DNA after cisplatin treatment of cancer patients. Int J Cancer 2006;119:2228-30
65. Pyun CW, Kim JH, Han KH, et al. In vivo protective effects of dietary curcumin and capsaicin against alcoholinduced oxidative stress. Biofactors 2014. [Epub ahead of print
66. Wang YT, Liu HS, Su CL. Curcumin-enhanced chemosensitivity of FDA-approved platinum (II)-based anticancer drugs involves downregulation of nuclear endonuclease G and NF-kappaB as well as induction of apoptosis and G2/M arrest. Int J Food Sci Nutr 2014;65:368-74
67. Notarbartolo M, Poma P, Perri D, et al. Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression. Cancer Lett 2005;224:53-65
68. Liu P, Kimmoun E, Legrand A, et al. Activation of NF-kappa B, AP-1 and STAT transcription factors is a frequent and early event in human hepatocellular carcinomas. J Hepatol 2002;37:63-71
69. Lev-Ari S, Starr A, Katzburg S, et al. Curcumin induces apoptosis and inhibits growth of orthotopic human non-small cell lung cancer xenografts. J Nutr Biochem 2014;25:843-50
70. Wang LH, Xiang J, Yan M, et al. The mitotic kinase Aurora-A induces mammary cell migration and breast cancer metastasis by activating the Cofilin-F-actin pathway. Cancer Res 2010;70:9118-28
71. Ke CS, Liu HS, Yen CH, et al. Curcumin-induced Aurora-A suppression not only causes mitotic defect and cell cycle arrest but also alters chemosensitivity to anticancer drugs. J Nutr Biochem 2014;25:526-39
72. Chanvorachote P, Nimmannit U, Stehlik C, et al. Nitric oxide regulates cell sensitivity to cisplatin-induced apoptosis through S-nitrosylation and inhibition of Bcl-2 ubiquitination. Cancer Res 2006;66:6353-60
73. Chanvorachote P, Pongrakhananon V, Wannachaiyasit S, et al. Curcumin sensitizes lung cancer cells to cisplatininduced apoptosis through superoxide anion-mediated Bcl-2 degradation. Cancer Invest 2009;27:624-35
74. Chen J, Wanming D, Zhang D, et al. Water-soluble antioxidants improve the antioxidant and anticancer activity of low concentrations of curcumin in human leukemia cells. Pharmazie 2005;60:57-61
75. El-Azab M, Hishe H, Moustafa Y, El-Awady S. Anti-angiogenic effect of resveratrol or curcumin in Ehrlich ascites carcinoma-bearing mice. Eur J Pharmacol 2011;652:7-14
76. Rak S, Cimbora-Zovko T, Gajski G, et al. Carboplatin resistant human laryngeal carcinoma cells are cross resistant to curcumin due to reduced curcumin accumulation. Toxicol in vitro 2013;27:523-32
77. Li L, Ahmed B, Mehta K, Kurzrock R. Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer. Mol Cancer Ther 2007;6:1276-82
78. Howells LM, Sale S, Sriramareddy SN, et al. Curcumin ameliorates oxaliplatininduced chemoresistance in HCT116 colorectal cancer cells in vitro and in vivo. Int J Cancer 2011;129:476-86
79. Beevers CS, Zhou H, Huang S. Hitting the golden TORget: curcumin's effects on mTOR signaling. Anticancer Agents Med Chem 2013;13:988-94
80. Ma J, Meng Y, Kwiatkowski DJ, et al. Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade. J Clin Invest 2010;120:103-14
81. Fimognari C, Turrini E, Ferruzzi L, et al. Natural isothiocyanates: genotoxic potential versus chemoprevention. Mutat Res 2012;750:107-31
82. Fimognari C, Hrelia P. Sulforaphane as a promising molecule for fighting cancer. Mutat Res 2007;635:90-104
83. Minarini A, Milelli A, Fimognari C, et al. Exploring the effects of isothiocyanates on chemotherapeutic drugs. Expert Opin Drug Metab Toxicol 2014;10:25-38
84. Chiao JW, Chung FL, Kancherla R, et al. Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells. Int J Oncol 2002;20:631-6
85. Gingras D, Gendron M, Boivin D, et al. Induction of medulloblastoma cell apoptosis by sulforaphane, a dietary anticarcinogen from Brassica vegetables. Cancer Lett 2004;203:35-43
86. Pham NA, Jacobberger JW, Schimmer AD, et al. The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice. Mol Cancer Ther 2004;3:1239-48
87. Karmakar S, Weinberg MS, Banik NL, et al. Activation of multiple molecular mechanisms for apoptosis in human malignant glioblastoma T98G and U87MG cells treated with sulforaphane. Neuroscience 2006;141:1265-80
88. Jackson SJ, Singletary KW. Sulforaphane: a naturally occurring mammary carcinoma mitotic inhibitor, which disrupts tubulin polymerization. Carcinogenesis 2004;25:219-27
89. Sestili P, Paolillo M, Lenzi M, et al. Sulforaphane induces DNA single strand breaks in cultured human cells. Mutat Res 2010;689:65-73
90. Park HS, Han MH, Kim GY, et al. Sulforaphane induces reactive oxygen species-mediated mitotic arrest and subsequent apoptosis in human bladder cancer 5637 cells. Food Chem Toxicol 2014;64:157-65
91. Clarke JD, Hsu A, Yu Z, et al. Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Mol Nutr Food Res 2011;55:999-1009
92. Singh AV, Xiao D, Lew KL, et al. Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis 2004;25:83-90
93. Cheung KL, Kong AN. Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention. AAPS J 2010;12:87-97
94. Wang XF, Wu DM, Li BX, et al. Synergistic inhibitory effect of sulforaphane and 5-fluorouracil in high and low metastasis cell lines of salivary gland adenoid cystic carcinoma. Phytother Res 2009;23:303-7
95. Milczarek M, Misiewicz-Krzeminska I, Lubelska K, Wiktorska K. Combination treatment with 5-fluorouracil and isothiocyanates shows an antagonistic effect in Chinese hamster fibroblast cells line-V79. Acta Pol Pharm 2011;68:331-42
96. Kallifatidis G, Labsch S, Rausch V, et al. Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate. Mol Ther 2011;19:188-95
97. Kaminski BM, Weigert A, Brune B, et al. Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death. Cancer Chemother Pharmacol 2011;67:1167-78
98. Pinz S, Unser S, Rascle A. The Natural Chemopreventive Agent Sulforaphane Inhibits STAT5 Activity. PLoS One 2014;9:e99391
99. Hong X, Chen G, Wang M, et al. STAT5a-targeting miRNA enhances chemosensitivity to cisplatin and 5-fluorouracil in human colorectal cancer cells. Mol Med Rep 2012;5:1215-19
100. Hunakova L, Gronesova P, Horvathova E, et al. Modulation of cisplatin sensitivity in human ovarian carcinoma A2780 and SKOV3 cell lines by sulforaphane. Toxicol Lett 2014;230(3):479-86
101. Suppipat K, Park CS, Shen Y, et al. Sulforaphane induces cell cycle arrest and apoptosis in acute lymphoblastic leukemia cells. PLoS One 2012;7:e51251
102. Shoba G, Joy D, Joseph T, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998;64:353-6
103. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J 2013;15:195-218
104. Kanai M, Yoshimura K, Asada M, et al. A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol 2011;68:157-64
105. Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001;21:2895-900
106. Giehl M, Leitner A, Haferlach C, et al. Detection of centrosome aberrations in disease-unrelated cells from patients with tumor treated with tyrosine kinase inhibitors. Eur J Haematol 2010;85:139-48
107. Urbina-Cano P, Bobadilla-Morales L, Ramirez-Herrera MA, et al. DNA damage in mouse lymphocytes exposed to curcumin and copper. J Appl Genet 2006;47:377-82
108. Kelly MR, Xu J, Alexander KE, Loo G. Disparate effects of similar phenolic phytochemicals as inhibitors of oxidative damage to cellular DNA. Mutat Res 2001;485:309-18
109. Cao J, Jia L, Zhou HM, et al. Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells. Toxicol Sci 2006;91:476-83
110. Blasiak J, Trzeciak A, Kowalik J. Curcumin damages DNA in human gastric mucosa cells and lymphocytes. J Environ Pathol Toxicol Oncol 1999;18:271-6
111. Sebastia N, Soriano JM, Barquinero JF, et al. In vitro cytogenetic and genotoxic effects of curcumin on human peripheral blood lymphocytes. Food Chem Toxicol 2012;50:3229-33
112. Sakano K, Kawanishi S. Metal-mediated DNA damage induced by curcumin in the presence of human cytochrome P450 isozymes. Arch Biochem Biophys 2002;405:223-30
113. Sun B, Ross SM, Trask OJ, et al. Assessing dose-dependent differences in DNA-damage, p53 response and genotoxicity for quercetin and curcumin. Toxicol In Vitro 2013;27:1877-87
114. National Toxicology Program. NTP toxicology and carcinogenesis studies of turmeric oleoresin (CAS No. 8024-37-1) (Major Component 79%-85% Curcumin, CAS No. 458-37-7) in F344/N Rats and B6C3F1 Mice (Feed Studies). Natl Toxicol Program Tech Rep Ser 1993;427:1-275
115. Martin-Cordero C, Lopez-Lazaro M, Galvez M, Ayuso MJ. Curcumin as a DNA topoisomerase II poison. J Enzyme Inhib Med Chem 2003;18:505-9
116. Lopez-Lazaro M. Anticancer and carcinogenic properties of curcumin: considerations for its clinical development as a cancer chemopreventive and chemotherapeutic agent. Mol Nutr Food Res 2008;52(Suppl 1):S103-27
117. Burgos-Moron E, Calderon-Montano JM, Salvador J, et al. The dark side of curcumin. Int J Cancer 2010;126:1771-5
118. Jaramillo MC, Zhang DD. The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev 2013;27:2179-91
119. Slocum SL, Kensler TW. Nrf2: control of sensitivity to carcinogens. Arch Toxicol 2011;85:273-84
120. Sak K. Chemotherapy and dietary phytochemical agents. Chemother Res Pract 2012;2012:282570