Cancer Treatment Reviews
Volume 35, Issue 7 , Pages 597-607 , November 2009

Harnessing the fruits of nature for the development of multi-targeted cancer therapeutics

  • Fazlul H. Sarkar

      Affiliations

    • Corresponding Author InformationCorresponding author. Address: Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 740 Hudson Webber Cancer Research Center, 4100 John R, Detroit, MI 48201, USA. Tel.: +1 313 576 8327; fax: +1 313 576 8389.
  • ,
  • Yiwei Li

      Affiliations

    • Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 715 Hudson Webber Cancer Research Center, 4100 John R, Detroit, MI 48201, USA. Tel.: +1 313 576 8318; fax: +1 313 576 8389.

Received 8 June 2009 ,Revised 30 June 2009 ,Accepted 2 July 2009.

References 

  1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96
  2. Lee MM, Gomez SL, Chang JS, Wey M, Wang RT, Hsing AW. Soy and isoflavone consumption in relation to prostate cancer risk in China. Cancer Epidemiol Biomarkers Prev. 2003;12:665–668
  3. Smith-Warner SA, Spiegelman D, Yaun SS, et al. Fruits, vegetables and lung cancer: a pooled analysis of cohort studies. Int J Cancer. 2003;107:1001–1011
  4. Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 2003;3:768–780
  5. Khan N, Afaq F, Mukhtar H. Apoptosis by dietary factors: the suicide solution for delaying cancer growth. Carcinogenesis. 2007;28:233–239
  6. Sarkar FH, Li Y, Wang Z, Kong D. Cellular signaling perturbation by natural products. Cell Signal 2009.
  7. Sarkar FH, Li YW. Targeting multiple signal pathways by chemopreventive agents for cancer prevention and therapy. Acta Pharmacol Sin. 2007;28:1305–1315
  8. Hamilton-Reeves JM, Rebello SA, Thomas W, Slaton JW, Kurzer MS. Isoflavone-rich soy protein isolate suppresses androgen receptor expression without altering estrogen receptor-beta expression or serum hormonal profiles in men at high risk of prostate cancer. J Nutr. 2007;137:1769–1775
  9. Pendleton JM, Tan WW, Anai S, et al. Phase II trial of isoflavone in prostate-specific antigen recurrent prostate cancer after previous local therapy. BMC Cancer. 2008;8:132
  10. Vaishampayan U, Hussain M, Banerjee M, et al. Lycopene and soy isoflavones in the treatment of prostate cancer. Nutr Cancer. 2007;59:1–7
  11. Bemis DL, Katz AE, Buttyan R. Clinical trials of natural products as chemopreventive agents for prostate cancer. Expert Opin Investig Drugs. 2006;15:1191–1200
  12. Dhillon N, Aggarwal BB, Newman RA, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008;14:4491–4499
  13. Naik R, Nixon S, Lopes A, Godfrey K, Hatem MH, Monaghan JM. A randomized phase II trial of indole-3-carbinol in the treatment of vulvar intraepithelial neoplasia. Int J Gynecol Cancer. 2006;16:786–790
  14. Barnes S. The chemopreventive properties of soy isoflavonoids in animal models of breast cancer. Breast Cancer Res Treat. 1997;46:169–179
  15. Dixon RA, Genistein Ferreira D. Phytochemistry. 2002;60:205–211
  16. Li Y, Sarkar FH. Down-regulation of invasion and angiogenesis-related genes identified by cDNA microarray analysis of PC3 prostate cancer cells treated with genistein. Cancer Lett. 2002;186:157–164
  17. Chinni SR, Li Y, Upadhyay S, Koppolu PK, Sarkar FH. Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells. Oncogene. 2001;20:2927–2936
  18. Li Y, Li X, Sarkar FH. Gene expression profiles of I3C- and DIM-treated PC3 human prostate cancer cells determined by cDNA microarray analysis. J Nutr. 2003;133:1011–1019
  19. Mukhopadhyay A, Bueso-Ramos C, Chatterjee D, Pantazis P, Aggarwal BB. Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines. Oncogene. 2001;20:7597–7609
  20. Shao ZM, Shen ZZ, Liu CH, et al. Curcumin exerts multiple suppressive effects on human breast carcinoma cells. Int J Cancer. 2002;98:234–240
  21. Davis JN, Kucuk O, Sarkar FH. Genistein inhibits NF-kappa B activation in prostate cancer cells. Nutr Cancer. 1999;35:167–174
  22. Chen CC, Sun YT, Chen JJ, Chiu KT. TNF-alpha-induced cyclooxygenase-2 expression in human lung epithelial cells: involvement of the phospholipase C-gamma 2, protein kinase C-alpha, tyrosine kinase, NF-kappa B-inducing kinase, and I-kappa B kinase 1/2 pathway. J Immunol. 2000;165:2719–2728
  23. Natarajan K, Manna SK, Chaturvedi MM, Aggarwal BB. Protein tyrosine kinase inhibitors block tumor necrosis factor-induced activation of nuclear factor-kappa B, degradation of IkappaBalpha, nuclear translocation of p65, and subsequent gene expression. Arch Biochem Biophys. 1998;352:59–70
  24. Li Y, Ahmed F, Ali S, Philip PA, Kucuk O, Sarkar FH. Inactivation of nuclear factor kappa B by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells. Cancer Res. 2005;65:6934–6942
  25. Li Y, Sarkar FH. Inhibition of nuclear factor kappa B activation in PC3 cells by genistein is mediated via Akt signaling pathway. Clin Cancer Res. 2002;8:2369–2377
  26. Gong L, Li Y, Nedeljkovic-Kurepa A, Sarkar FH. Inactivation of NF-kappa B by genistein is mediated via Akt signaling pathway in breast cancer cells. Oncogene. 2003;22:4702–4709
  27. Akiyama T, Ishida J, Nakagawa S, et al. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem. 1987;262:5592–5595
  28. Li Y, Wang Z, Kong D, Li R, Sarkar SH, Sarkar FH. Regulation of Akt/FOXO3a/GSK-3beta/AR signaling network by isoflavone in prostate cancer cells. J Biol Chem. 2008;283:27707–27716
  29. Su Y, Simmen FA, Xiao R, Simmen RC. Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in dietary protection from mammary tumors. Physiol Genomics. 2007;30:8–16
  30. Su Y, Simmen RC. Soy isoflavone genistein upregulates epithelial adhesion molecule E-cadherin expression and attenuates beta-catenin signaling in mammary epithelial cells. Carcinogenesis. 2009;30:331–339
  31. Wang Z, Zhang Y, Li Y, Banerjee S, Liao J, Sarkar FH. Down-regulation of Notch-1 contributes to cell growth inhibition and apoptosis in pancreatic cancer cells. Mol Cancer Ther. 2006;5:483–493
  32. Wang Z, Zhang Y, Banerjee S, Li Y, Sarkar FH. Inhibition of nuclear factor kappa b activity by genistein is mediated via Notch-1 signaling pathway in pancreatic cancer cells. Int J Cancer. 2006;118:1930–1936
  33. Davis JN, Muqim N, Bhuiyan M, Kucuk O, Pienta KJ, Sarkar FH. Inhibition of prostate specific antigen expression by genistein in prostate cancer cells. Int J Oncol. 2000;16:1091–1097
  34. Davis JN, Kucuk O, Sarkar FH. Expression of prostate-specific antigen is transcriptionally regulated by genistein in prostate cancer cells. Mol Carcinog. 2002;34:91–101
  35. Fritz WA, Wang J, Eltoum IE, Lamartiniere CA. Dietary genistein down-regulates androgen and estrogen receptor expression in the rat prostate. Mol Cell Endocrinol. 2002;186:89–99
  36. Sharma OP, Adlercreutz H, Strandberg JD, Zirkin BR, Coffey DS, Ewing LL. Soy of dietary source plays a preventive role against the pathogenesis of prostatitis in rats. J Steroid Biochem Mol Biol. 1992;43:557–564
  37. Onozawa M, Kawamori T, Baba M, et al. Effects of a soybean isoflavone mixture on carcinogenesis in prostate and seminal vesicles of F344 rats. Jpn J Cancer Res. 1999;90:393–398
  38. Landstrom M, Zhang JX, Hallmans G, et al. Inhibitory effects of soy and rye diets on the development of Dunning R3327 prostate adenocarcinoma in rats. Prostate. 1998;36:151–161
  39. Zhou JR, Gugger ET, Tanaka T, Guo Y, Blackburn GL, Clinton SK. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice. J Nutr. 1999;129:1628–1635
  40. Li D, Yee JA, McGuire MH, Murphy PA, Yan L. Soybean isoflavones reduce experimental metastasis in mice. J Nutr. 1999;129:1075–1078
  41. Lamartiniere CA, Moore JB, Brown NM, Thompson R, Hardin MJ, Barnes S. Genistein suppresses mammary cancer in rats. Carcinogenesis. 1995;16:2833–2840
  42. Uckun FM, Evans WE, Forsyth CJ, et al. Biotherapy of B-cell precursor leukemia by targeting genistein to CD19-associated tyrosine kinases. Science. 1995;267:886–891
  43. Wei H, Wei L, Frenkel K, Bowen R, Barnes S. Inhibition of tumor promoter-induced hydrogen peroxide formation in vitro and in vivo by genistein. Nutr Cancer. 1993;20:1–12
  44. Kameoka S, Leavitt P, Chang C, Kuo SM. Expression of antioxidant proteins in human intestinal Caco-2 cells treated with dietary flavonoids. Cancer Lett. 1999;146:161–167
  45. Davis JN, Kucuk O, Djuric Z, Sarkar FH. Soy isoflavone supplementation in healthy men prevents NF-kappa B activation by TNF-alpha in blood lymphocytes. Free Radic Biol Med. 2001;30:1293–1302
  46. Hussain M, Banerjee M, Sarkar FH, et al. Soy isoflavones in the treatment of prostate cancer. Nutr Cancer. 2003;47:111–117
  47. Pendleton JM, Tan WW, Anai S, et al. Phase II trial of isoflavone in prostate-specific antigen recurrent prostate cancer after previous local therapy. BMC Cancer. 2008;8:132
  48. Hamilton-Reeves JM, Rebello SA, Thomas W, Slaton JW, Kurzer MS. Isoflavone-rich soy protein isolate suppresses androgen receptor expression without altering estrogen receptor-beta expression or serum hormonal profiles in men at high risk of prostate cancer. J Nutr. 2007;137:1769–1775
  49. Joniau S, Goeman L, Roskams T, Lerut E, Oyen R, Van PH. Effect of nutritional supplement challenge in patients with isolated high-grade prostatic intraepithelial neoplasia. Urology. 2007;69:1102–1106
  50. Kumar NB, Cantor A, Allen K, et al. The specific role of isoflavones in reducing prostate cancer risk. Prostate. 2004;59:141–147
  51. Vere White RW, Hackman RM, Soares SE, Beckett LA, Li Y, Sun B. Effects of a genistein-rich extract on PSA levels in men with a history of prostate cancer. Urology. 2004;63:259–263
  52. Adams KF, Chen C, Newton KM, Potter JD, Lampe JW. Soy isoflavones do not modulate prostate-specific antigen concentrations in older men in a randomized controlled trial. Cancer Epidemiol Biomarkers Prev. 2004;13:644–648
  53. Martin PM, Horwitz KB, Ryan DS, McGuire WL. Phytoestrogen interaction with estrogen receptors in human breast cancer cells. Endocrinology. 1978;103:1860–1867
  54. Messina MJ, Wood CE. Soy isoflavones, estrogen therapy, and breast cancer risk: analysis and commentary. Nutr J. 2008;7:17
  55. Lampe JW, Nishino Y, Ray RM, et al. Plasma isoflavones and fibrocystic breast conditions and breast cancer among women in Shanghai, China. Cancer Epidemiol Biomarkers Prev. 2007;16:2579–2586
  56. Dai Q, Franke AA, Yu H, et al. Urinary phytoestrogen excretion and breast cancer risk: evaluating potential effect modifiers endogenous estrogens and anthropometrics. Cancer Epidemiol Biomarkers Prev. 2003;12:497–502
  57. Sartippour MR, Rao JY, Apple S, et al. A pilot clinical study of short-term isoflavone supplements in breast cancer patients. Nutr Cancer. 2004;49:59–65
  58. Kumar NB, Cantor A, Allen K, Riccardi D, Cox CE. The specific role of isoflavones on estrogen metabolism in premenopausal women. Cancer. 2002;94:1166–1174
  59. Bobe G, Sansbury LB, Albert PS, et al. Dietary flavonoids and colorectal adenoma recurrence in the polyp prevention trial. Cancer Epidemiol Biomarkers Prev. 2008;17:1344–1353
  60. Adams KF, Lampe PD, Newton KM, et al. Soy protein containing isoflavones does not decrease colorectal epithelial cell proliferation in a randomized controlled trial. Am J Clin Nutr. 2005;82:620–626
  61. Ahmad IU, Forman JD, Sarkar F, et al. Reduction of adverse events by soy isoflavones in patients undergoing external beam radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2009;72:S318
  62. Verhoeven DT, Verhagen H, Goldbohm RA, van den Brandt PA, van PG. A review of mechanisms underlying anticarcinogenicity by brassica vegetables. Chem Biol Interact. 1997;103:79–129
  63. Dashwood RH, Fong AT, Arbogast DN, Bjeldanes LF, Hendricks JD, Bailey GS. Anticarcinogenic activity of indole-3-carbinol acid products: ultrasensitive bioassay by trout embryo microinjection. Cancer Res. 1994;54:3617–3619
  64. Bhuiyan MM, Li Y, Banerjee S, et al. Down-regulation of androgen receptor by 3,3’-diindolylmethane contributes to inhibition of cell proliferation and induction of apoptosis in both hormone-sensitive LNCaP and insensitive C4–2B prostate cancer cells. Cancer Res. 2006;66:10064–10072
  65. Li Y, Chinni SR, Sarkar FH. Selective growth regulatory and pro-apoptotic effects of DIM is mediated by AKT and NF-kappa B pathways in prostate cancer cells. Front Biosci. 2005;10:236–243
  66. Chinni SR, Sarkar FH. Akt inactivation is a key event in indole-3-carbinol-induced apoptosis in PC-3 cells. Clin Cancer Res. 2002;8:1228–1236
  67. Leong H, Riby JE, Firestone GL, Bjeldanes LF. Potent ligand-independent estrogen receptor activation by 3,3’-diindolylmethane is mediated by cross talk between the protein kinase A and mitogen-activated protein kinase signaling pathways. Mol Endocrinol. 2004;18:291–302
  68. Li Y, Wang Z, Kong D, et al. Regulation of FOXO3a/beta-catenin/GSK-3beta signaling by 3, 3’-diindolylmethane contributes to inhibition of cell proliferation and induction of apoptosis in prostate cancer cells. J Biol Chem. 2007;282:21542–21550
  69. Le HT, Schaldach CM, Firestone GL, Bjeldanes LF. Plant-derived 3,3′-diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem. 2003;278:21136–21145
  70. Bradlow HL, Michnovicz J, Telang NT, Osborne MP. Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice. Carcinogenesis. 1991;12:1571–1574
  71. Kojima T, Tanaka T, Mori H. Chemoprevention of spontaneous endometrial cancer in female Donryu rats by dietary indole-3-carbinol. Cancer Res. 1994;54:1446–1449
  72. Manson MM, Hudson EA, Ball HW, et al. Chemoprevention of aflatoxin B1-induced carcinogenesis by indole-3-carbinol in rat liver–predicting the outcome using early biomarkers. Carcinogenesis. 1998;19:1829–1836
  73. Stresser DM, Bailey GS, Williams DE. Indole-3-carbinol and beta-naphthoflavone induction of aflatoxin B1 metabolism and cytochromes P-450 associated with bioactivation and detoxication of aflatoxin B1 in the rat. Drug Metab Dispos. 1994;22:383–391
  74. Bradfield CA, Bjeldanes LF. Effect of dietary indole-3-carbinol on intestinal and hepatic monooxygenase, glutathione S-transferase and epoxide hydrolase activities in the rat. Food Chem Toxicol. 1984;22:977–982
  75. Souli E, Machluf M, Morgenstern A, Sabo E, Yannai S. Indole-3-carbinol (I3C) exhibits inhibitory and preventive effects on prostate tumors in mice. Food Chem Toxicol. 2008;46:863–870
  76. Kassie F, Anderson LB, Scherber R, et al. Indole-3-carbinol inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone plus benzo(a)pyrene-induced lung tumorigenesis in A/J mice and modulates carcinogen-induced alterations in protein levels. Cancer Res. 2007;67:6502–6511
  77. Oganesian A, Hendricks JD, Pereira CB, Orner GA, Bailey GS, Williams DE. Potency of dietary indole-3-carbinol as a promoter of aflatoxin B1-initiated hepatocarcinogenesis: results from a 9000 animal tumor study. Carcinogenesis. 1999;20:453–458
  78. Doppalapudi RS, Riccio ES, Rausch LL, et al. Evaluation of chemopreventive agents for genotoxic activity. Mutat Res. 2007;629:148–160
  79. Chang X, Tou JC, Hong C, et al. 3,3′-Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic mice. Carcinogenesis. 2005;26:771–778
  80. Kong D, Banerjee S, Huang W, et al. Mammalian target of rapamycin repression by 3,3′-diindolylmethane inhibits invasion and angiogenesis in platelet-derived growth factor-D-overexpressing PC3 cells. Cancer Res. 2008;68:1927–1934
  81. Kong D, Li Y, Wang Z, Banerjee S, Sarkar FH. Inhibition of angiogenesis and invasion by 3,3′-diindolylmethane is mediated by the nuclear factor-kappa B downstream target genes MMP-9 and uPA that regulated bioavailability of vascular endothelial growth factor in prostate cancer. Cancer Res. 2007;67:3310–3319
  82. Ali S, Banerjee S, Ahmad A, El-Rayes BF, Philip PA, Sarkar FH. Apoptosis-inducing effect of erlotinib is potentiated by 3,3’-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer. Mol Cancer Ther. 2008;7:1708–1719
  83. Nachshon-Kedmi M, Fares FA, Yannai S. Therapeutic activity of 3,3′-diindolylmethane on prostate cancer in an in vivo model. Prostate. 2004;61:153–160
  84. Reed GA, Peterson KS, Smith HJ, et al. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomarkers Prev. 2005;14:1953–1960
  85. Rosen CA, Bryson PC. Indole-3-carbinol for recurrent respiratory papillomatosis: long-term results. J Voice. 2004;18:248–253
  86. Reed GA, Sunega JM, Sullivan DK, et al. Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3’-diindolylmethane in healthy subjects. Cancer Epidemiol Biomarkers Prev. 2008;17:2619–2624
  87. Heath EI, Heilbrun LK, Vaishampayan UN, et al. A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3’-diindolylmethane) in castrate-resistant, non-metastatic, PSA relapse prostate cancer patients. 2009 Genitourinary Cancers Symposium 2009;Abstract 188.
  88. Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 2008;269:199–225
  89. Bharti AC, Donato N, Singh S, Aggarwal BB. Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood. 2003;101:1053–1062
  90. Hussain AR, Ahmed M, Al-Jomah NA, et al. Curcumin suppresses constitutive activation of nuclear factor-kappa B and requires functional Bax to induce apoptosis in Burkitt’s lymphoma cell lines. Mol Cancer Ther. 2008;7:3318–3329
  91. Kunnumakkara AB, Diagaradjane P, Guha S, et al. Curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting nuclear factor-kappa B-regulated gene products. Clin Cancer Res. 2008;14:2128–2136
  92. Wang D, Veena MS, Stevenson K, et al. Liposome-encapsulated curcumin suppresses growth of head and neck squamous cell carcinoma in vitro and in xenografts through the inhibition of nuclear factor kappa B by an AKT-independent pathway. Clin Cancer Res. 2008;14:6228–6236
  93. Milacic V, Banerjee S, Landis-Piwowar KR, Sarkar FH, Majumdar AP, Dou QP. Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo. Cancer Res. 2008;68:7283–7292
  94. Yu S, Shen G, Khor TO, Kim JH, Kong AN. Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism. Mol Cancer Ther. 2008;7:2609–2620
  95. Weir NM, Selvendiran K, Kutala VK, et al. Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK. Cancer Biol Ther. 2007;6:178–184
  96. Kumar AP, Garcia GE, Ghosh R, Rajnarayanan RV, Alworth WL, Slaga TJ. 4-Hydroxy-3-methoxybenzoic acid methyl ester: a curcumin derivative targets Akt/NF kappa B cell survival signaling pathway: potential for prostate cancer management. Neoplasia. 2003;5:255–266
  97. Squires MS, Hudson EA, Howells L, et al. Relevance of mitogen activated protein kinase (MAPK) and phosphotidylinositol-3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin in breast cells. Biochem Pharmacol. 2003;65:361–376
  98. Woo JH, Kim YH, Choi YJ, et al. Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis. 2003;24:1199–1208
  99. Anand P, Thomas SG, Kunnumakkara AB, et al. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem Pharmacol. 2008;76:1590–1611
  100. Sharma RA, Euden SA, Platton SL, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res. 2004;10:6847–6854
  101. Garcea G, Berry DP, Jones DJ, et al. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev. 2005;14:120–125
  102. Garcea G, Jones DJ, Singh R, et al. Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration. Br J Cancer. 2004;90:1011–1015
  103. Padhye S, Yang H, Jamadar A, et al. New Difluoro Knoevenagel Condensates of Curcumin, Their Schiff Bases and Copper Complexes as Proteasome Inhibitors and Apoptosis Inducers in Cancer Cells. Pharm Res 2009.
  104. Kim GY, Kim KH, Lee SH, et al. Curcumin inhibits immunostimulatory function of dendritic cells: MAPKs and translocation of NF-kappa B as potential targets. J Immunol. 2005;174:8116–8124
  105. Salh B, Assi K, Templeman V, et al. Curcumin attenuates DNB-induced murine colitis. Am J Physiol Gastrointest Liver Physiol. 2003;285:G235–G243
  106. Yan C, Jamaluddin MS, Aggarwal B, Myers J, Boyd DD. Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin. Mol Cancer Ther. 2005;4:233–241
  107. Ryu MJ, Cho M, Song JY, et al. Natural derivatives of curcumin attenuate the Wnt/beta-catenin pathway through down-regulation of the transcriptional coactivator p300. Biochem Biophys Res Commun. 2008;377:1304–1308
  108. Jaiswal AS, Marlow BP, Gupta N, Narayan S. Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene. 2002;21:8414–8427
  109. Nakamura K, Yasunaga Y, Segawa T, et al. Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines. Int J Oncol. 2002;21:825–830
  110. Ohtsu H, Xiao Z, Ishida J. Et al. Antitumor agents. 217. Curcumin analogues as novel androgen receptor antagonists with potential as anti-prostate cancer agents. J Med Chem. 2002;45:5037–5042
  111. Huang AC, Lin SY, Su CC, et al. Effects of curcumin on N-bis(2-hydroxypropyl) nitrosamine (DHPN)-induced lung and liver tumorigenesis in BALB/c mice in vivo. In vivo. 2008;22:781–785
  112. Li N, Chen X, Liao J, et al. Inhibition of 7, 12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters by tea and curcumin. Carcinogenesis. 2002;23:1307–1313
  113. Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappa B-regulated gene products. Cancer Res. 2007;67:3853–3861
  114. Cruz-Correa M, Shoskes DA, Sanchez P, et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2006;4:1035–1038
  115. 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;21:2895–2900

PII: S0305-7372(09)00095-4

doi: 10.1016/j.ctrv.2009.07.001

Cancer Treatment Reviews
Volume 35, Issue 7 , Pages 597-607 , November 2009