Cancer Letters
Volume 262, Issue 2 , Pages 153-163 , 18 April 2008

Indole-3-carbinol as a chemopreventive and anti-cancer agent

  • Jing-Ru Weng

      Affiliations

    • Department of Biological Science and Technology, China Medical University, Taiwan
    • Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung 40402, Taiwan
    • ,
  • Chen-Hsun Tsai

      Affiliations

    • Division of Medicinal Chemistry, College of Pharmacy, Parks Hall, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, USA
    • ,
  • Samuel K. Kulp

      Affiliations

    • Division of Medicinal Chemistry, College of Pharmacy, Parks Hall, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, USA
    • ,
  • Ching-Shih Chen

      Affiliations

    • Division of Medicinal Chemistry, College of Pharmacy, Parks Hall, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 614 688 4008; fax: +1 614 688 8556.

Received 8 December 2007 ,Revised 17 January 2008 ,Accepted 18 January 2008.

References 

  1. Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J. Natl. Cancer Inst. 2000;92:61–68
  2. Higdon JV, Delage B, Williams DE, Dashwood RH. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol. Res. 2007;55:224–236
  3. Minich DM, Bland JS. A review of the clinical efficacy and safety of cruciferous vegetable phytochemicals. Nutr. Rev. 2007;65:259–267
  4. Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol. Biomarkers Prev. 1996;5:733–748
  5. Hong C, Firestone GL, Bjeldanes LF. Bcl-2 family-mediated apoptotic effects of 3,3′-diindolylmethane (DIM) in human breast cancer cells. Biochem. Pharmacol. 2002;63:1085–1097
  6. Howells LM, Gallacher-Horley B, Houghton CE, Manson MM, Hudson EA. Indole-3-carbinol inhibits protein kinase B/Akt and induces apoptosis in the human breast tumor cell line MDA MB468 but not in the nontumorigenic HBL100 line. Mol. Cancer Ther. 2002;1:1161–1172
  7. Katdare M, Osborne MP, Telang NT. Inhibition of aberrant proliferation and induction of apoptosis in pre-neoplastic human mammary epithelial cells by natural phytochemicals. Oncol. Rep. 1998;5:311–315
  8. Rahman KM, Aranha O, Sarkar FH. Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in nontumorigenic breast epithelial cells. Nutr. Cancer. 2003;45:101–112
  9. Frydoonfar HR, McGrath DR, Spigelman AD. Inhibition of proliferation of a colon cancer cell line by indole-3-carbinol. Colorectal Dis. 2002;4:205–207
  10. Hudson EA, Howells LM, Gallacher-Horley B, Fox LH, Gescher A, Manson MM. Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line. BMC Cancer. 2003;3:2
  11. Zheng Q, Hirose Y, Yoshimi N, Murakami A, Koshimizu K, Ohigashi H, et al. Further investigation of the modifying effect of various chemopreventive agents on apoptosis and cell proliferation in human colon cancer cells. J. Cancer Res. Clin. Oncol. 2002;128:539–546
  12. 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
  13. Frydoonfar HR, McGrath DR, Spigelman AD. The effect of indole-3-carbinol and sulforaphane on a prostate cancer cell line. ANZ J. Surg. 2003;73:154–156
  14. Nachshon-Kedmi M, Yannai S, Haj A, Fares FA. Indole-3-carbinol and 3,3′-diindolylmethane induce apoptosis in human prostate cancer cells. Food Chem. Toxicol. 2003;41:745–752
  15. Leong H, Firestone GL, Bjeldanes LF. Cytostatic effects of 3,3′-diindolylmethane in human endometrial cancer cells result from an estrogen receptor-mediated increase in transforming growth factor-alpha expression. Carcinogenesis. 2001;22:1809–1817
  16. Aggarwal BB, Ichikawa H. Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle. 2005;4:1201–1215
  17. Aggarwal BB, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem. Pharmacol. 2006;71:1397–1421
  18. Kim YS, Milner JA. Targets for indole-3-carbinol in cancer prevention. J. Nutr. Biochem. 2005;16:65–73
  19. Rogan EG. The natural chemopreventive compound indole-3-carbinol: state of the science. In Vivo. 2006;20:221–228
  20. Sarkar FH, Li Y. Indole-3-carbinol and prostate cancer. J. Nutr. 2004;134:3493S–3498S
  21. 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
  22. Grubbs CJ, Steele VE, Casebolt T, Juliana MM, Eto I, Whitaker LM, et al. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer Res. 1995;15:709–716
  23. He YH, Friesen MD, Ruch RJ, Schut HA. Indole-3-carbinol as a chemopreventive agent in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) carcinogenesis: inhibition of PhIP-DNA adduct formation, acceleration of PhIP metabolism, and induction of cytochrome P450 in female F344 rats. Food Chem. Toxicol. 2000;38:15–23
  24. Jin L, Qi M, Chen DZ, Anderson A, Yang GY, Arbeit JM, et al. ;Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice. Cancer Res. 1999;59:3991–3997
  25. 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
  26. Oganesian A, Hendricks JD, Williams DE. Long term dietary indole-3-carbinol inhibits diethylnitrosamine-initiated hepatocarcinogenesis in the infant mouse model. Cancer Lett. 1997;118:87–94
  27. Yu Z, Mahadevan B, Lohr CV, Fischer KA, Louderback MA, Krueger SK, et al. Indole-3-carbinol in the maternal diet provides chemoprotection for the fetus against transplacental carcinogenesis by the polycyclic aromatic hydrocarbon dibenzo[a,l]pyrene. Carcinogenesis. 2006;27:2116–2123
  28. Bell MC, Crowley-Nowick P, Bradlow HL, Sepkovic DW, Schmidt-Grimminger D, Howell P, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol. Oncol. 2000;78:123–129
  29. Reed GA, Arneson DW, Putnam WC, Smith HJ, Gray JC, Sullivan DK, et al. Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3′-diindolylmethane. Cancer Epidemiol. Biomarkers Prev. 2006;15:2477–2481
  30. Reed GA, Peterson KS, Smith HJ, Gray JC, Sullivan DK, Mayo MS, et al. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol. Biomarkers Prev. 2005;14:1953–1960
  31. 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
  32. Rosen CA, Bryson PC. Indole-3-carbinol for recurrent respiratory papillomatosis: long-term results. J. Voice. 2004;18:248–253
  33. Grose KR, Bjeldanes LF. Oligomerization of indole-3-carbinol in aqueous acid. Chem. Res. Toxicol. 1992;5:188–193
  34. Anderton MJ, Jukes R, Lamb JH, Manson MM, Gescher A, Steward WP, et al. Liquid chromatographic assay for the simultaneous determination of indole-3-carbinol and its acid condensation products in plasma. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2003;787:281–291
  35. Anderton MJ, Manson MM, Verschoyle RD, Gescher A, Lamb JH, Farmer PB, et al. Pharmacokinetics and tissue disposition of indole-3-carbinol and its acid condensation products after oral administration to mice. Clin. Cancer Res. 2004;10:5233–5241
  36. De Kruif CA, Marsman JW, Venekamp JC, Falke HE, Noordhoek J, Blaauboer BJ, et al. Structure elucidation of acid reaction products of indole-3-carbinol: detection in vivo and enzyme induction in vitro. Chem. Biol. Interact. 1991;80:303–315
  37. Stresser DM, Williams DE, Griffin DA, Bailey GS. Mechanisms of tumor modulation by indole-3-carbinol. Disposition and excretion in male Fischer 344 rats. Drug Metab. Dispos. 1995;23:965–975
  38. Abdelrahim M, Newman K, Vanderlaag K, Samudio I, Safe S. 3,3′-diindolylmethane (DIM) and its derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5. Carcinogenesis. 2006;27:717–728
  39. Bhuiyan MM, Li Y, Banerjee S, Ahmed F, Wang Z, Ali 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
  40. Garikapaty VP, Ashok BT, Tadi K, Mittelman A, Tiwari RK. 3,3′-Diindolylmethane downregulates pro-survival pathway in hormone independent prostate cancer. Biochem. Biophys. Res. Commun. 2006;340:718–725
  41. 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-kappaB downstream target genes MMP-9 and uPA that regulated bioavailability of vascular endothelial growth factor in prostate cancer. Cancer Res. 2007;67:3310–3319
  42. 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
  43. Li Y, Wang Z, Kong D, Murthy S, Dou QP, Sheng S, 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
  44. Nachshon-Kedmi M, Yannai S, Fares FA. Induction of apoptosis in human prostate cancer cell line, PC3, by 3,3′-diindolylmethane through the mitochondrial pathway. Br. J. Cancer. 2004;91:1358–1363
  45. Rahman KW, Ali S, Aboukameel A, Sarkar SH, Wang Z, Philip PA, et al. Inactivation of NF-{kappa}B by 3,3′-diindolylmethane contributes to increased apoptosis induced by chemotherapeutic agent in breast cancer cells. Mol. Cancer Ther. 2007;6:2757–2765
  46. Rahman KW, Li Y, Wang Z, Sarkar SH, Sarkar FH. Gene expression profiling revealed survivin as a target of 3,3′-diindolylmethane-induced cell growth inhibition and apoptosis in breast cancer cells. Cancer Res. 2006;66:4952–4960
  47. Herrmann S, Seidelin M, Bisgaard HC, Vang O. Indolo[3,2-b]carbazole inhibits gap junctional intercellular communication in rat primary hepatocytes and acts as a potential tumor promoter. Carcinogenesis. 2002;23:1861–1868
  48. Liu H, Wormke M, Safe SH, Bjeldanes LF. Indolo[3,2-b]carbazole: a dietary-derived factor that exhibits both antiestrogenic and estrogenic activity. J. Natl. Cancer Inst. 1994;86:1758–1765
  49. Brandi G, Paiardini M, Cervasi B, Fiorucci C, Filippone P, De Marco C, et al. A new indole-3-carbinol tetrameric derivative inhibits cyclin-dependent kinase 6 expression, and induces G1 cell cycle arrest in both estrogen-dependent and estrogen-independent breast cancer cell lines. Cancer Res. 2003;63:4028–4036
  50. Firestone GL, Bjeldanes LF. Indole-3-carbinol and 3-3′-diindolylmethane antiproliferative signaling pathways control cell-cycle gene transcription in human breast cancer cells by regulating promoter-Sp1 transcription factor interactions. J. Nutr. 2003;133:2448S–2455S
  51. Mulvey L, Chandrasekaran A, Liu K, Lombardi S, Wang XP, Auborn KJ, et al. Interplay of genes regulated by estrogen and diindolylmethane in breast cancer cell lines. Mol. Med. 2007;13:69–78
  52. Chang YC, Riby J, Chang GH, Peng BC, Firestone G, Bjeldanes LF. Cytostatic and antiestrogenic effects of 2-(indol-3-ylmethyl)-3,3′-diindolylmethane, a major in vivo product of dietary indole-3-carbinol. Biochem. Pharmacol. 1999;58:825–834
  53. Riby JE, Feng C, Chang YC, Schaldach CM, Firestone GL, Bjeldanes LF. The major cyclic trimeric product of indole-3-carbinol is a strong agonist of the estrogen receptor signaling pathway. Biochemistry. 2000;39:910–918
  54. Auborn KJ, Fan S, Rosen EM, Goodwin L, Chandraskaren A, Williams DE, et al. Indole-3-carbinol is a negative regulator of estrogen. J. Nutr. 2003;133:2470S–2475S
  55. Wang TT, Milner MJ, Milner JA, Kim YS. Estrogen receptor alpha as a target for indole-3-carbinol. J. Nutr. Biochem. 2006;17:659–664
  56. Parkin DR, Malejka-Giganti D. Differences in the hepatic P450-dependent metabolism of estrogen and tamoxifen in response to treatment of rats with 3,3′-diindolylmethane and its parent compound indole-3-carbinol. Cancer Detect. Prev. 2004;28:72–79
  57. Rahman KW, Sarkar FH. Inhibition of nuclear translocation of nuclear factor-{kappa}B contributes to 3,3′-diindolylmethane-induced apoptosis in breast cancer cells. Cancer Res. 2005;65:364–371
  58. Takada Y, Andreeff M, Aggarwal BB. Indole-3-carbinol suppresses NF-kappaB and IkappaBalpha kinase activation, causing inhibition of expression of NF-kappaB-regulated antiapoptotic and metastatic gene products and enhancement of apoptosis in myeloid and leukemia cells. Blood. 2005;106:641–649
  59. Bellacosa A, Kumar CC, Di Cristofano A, Testa JR. Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv. Cancer Res. 2005;94:29–86
  60. Chen YL, Law PY, Loh HH. Inhibition of PI3K/Akt signaling: an emerging paradigm for targeted cancer therapy. Curr. Med. Chem. Anticancer Agents. 2005;5:575–589
  61. Cheng JQ, Lindsley CW, Cheng GZ, Yang H, Nicosia SV. The Akt/PKB pathway: molecular target for cancer drug discovery. Oncogene. 2005;24:7482–7492
  62. Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat. Rev. Drug Discov. 2005;4:988–1004
  63. Kim D, Cheng GZ, Lindsley CW, Yang H, Cheng JQ. Targeting the phosphatidylinositol-3 kinase/Akt pathway for the treatment of cancer. Curr. Opin. Investig. Drugs. 2005;6:1250–1258
  64. Yoeli-Lerner M, Toker A. Akt/PKB signaling in cancer: a function in cell motility and invasion. Cell Cycle. 2006;5:603–605
  65. Aggarwal BB. Nuclear factor-kappaB: the enemy within. Cancer Cell. 2004;6:203–208
  66. Weng JR, Tsai CH, Kulp SK, Wang D, Lin CH, Yang HC, et al. A potent indole-3-carbinol derived antitumor agent with pleiotropic effects on multiple signaling pathways in prostate cancer cells. Cancer Res. 2007;67:7815–7824
  67. Lian JP, Word B, Taylor S, Hammons GJ, Lyn-Cook BD. Modulation of the constitutive activated STAT3 transcription factor in pancreatic cancer prevention: effects of indole-3-carbinol (I3C) and genistein. Anticancer Res. 2004;24:133–137
  68. 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
  69. Cover CM, Hsieh SJ, Tran SH, Hallden G, Kim GS, Bjeldanes LF, et al. Indole-3-carbinol inhibits the expression of cyclin-dependent kinase-6 and induces a G1 cell cycle arrest of human breast cancer cells independent of estrogen receptor signaling. J. Biol. Chem. 1998;273:3838–3847
  70. Cram EJ, Liu BD, Bjeldanes LF, Firestone GL. Indole-3-carbinol inhibits CDK6 expression in human MCF-7 breast cancer cells by disrupting Sp1 transcription factor interactions with a composite element in the CDK6 gene promoter. J. Biol. Chem. 2001;276:22332–22340
  71. Hong C, Kim HA, Firestone GL, Bjeldanes LF. 3,3′-Diindolylmethane (DIM) induces a G(1) cell cycle arrest in human breast cancer cells that is accompanied by Sp1-mediated activation of p21(WAF1/CIP1) expression. Carcinogenesis. 2002;23:1297–1305
  72. Garcia HH, Brar GA, Nguyen DH, Bjeldanes LF, Firestone GL. Indole-3-carbinol (I3C) inhibits cyclin-dependent kinase-2 function in human breast cancer cells by regulating the size distribution, associated cyclin E forms, and subcellular localization of the CDK2 protein complex. J. Biol. Chem. 2005;280:8756–8764
  73. Bjeldanes LF, Kim JY, Grose KR, Bartholomew JC, Bradfield CA. Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Proc. Natl. Acad. Sci. USA. 1991;88:9543–9547
  74. Kohle C, Bock KW. Coordinate regulation of Phase I and II xenobiotic metabolisms by the Ah receptor and Nrf2. Biochem. Pharmacol. 2007;73:1853–1862
  75. Ociepa-Zawal M, Rubis B, Lacinski M, Trzeciak WH. The effect of indole-3-carbinol on the expression of CYP1A1, CYP1B1 and AhR genes and proliferation of MCF-7 cells. Acta Biochim. Pol. 2007;54:113–117
  76. Dashwood RH. Indole-3-carbinol: anticarcinogen or tumor promoter in brassica vegetables?. Chem. Biol. Interact. 1998;110:1–5
  77. Larsen-Su SA, Williams DE. Transplacental exposure to indole-3-carbinol induces sex-specific expression of CYP1A1 and CYP1B1 in the liver of Fischer 344 neonatal rats. Toxicol. Sci. 2001;64:162–168
  78. Bradlow HL, Sepkovic DW, Telang NT, Osborne MP. Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Ann. N.Y. Acad. Sci. 1999;889:204–213
  79. Newfield L, Goldsmith A, Bradlow HL, Auborn K. Estrogen metabolism and human papillomavirus-induced tumors of the larynx: chemo-prophylaxis with indole-3-carbinol. Anticancer Res. 1993;13:337–341
  80. Greenwald P. Clinical trials in cancer prevention: current results and perspectives for the future. J. Nutr. 2004;134:3507S–3512S
  81. Ashok BT, Chen YG, Liu X, Garikapaty VP, Seplowitz R, Tschorn J, et al. Multiple molecular targets of indole-3-carbinol, a chemopreventive anti-estrogen in breast cancer. Eur. J. Cancer Prev. 2002;11(Suppl. 2):S86–S93
  82. Cover CM, Hsieh SJ, Cram EJ, Hong C, Riby JE, Bjeldanes LF, et al. Indole-3-carbinol and tamoxifen cooperate to arrest the cell cycle of MCF-7 human breast cancer cells. Cancer Res. 1999;59:1244–1251
  83. Sundar SN, Kerekatte V, Equinozio CN, Doan VB, Bjeldanes LF, Firestone GL. Indole-3-carbinol selectively uncouples expression and activity of estrogen receptor subtypes in human breast cancer cells. Mol. Endocrinol. 2006;20:3070–3082
  84. Carter TH, Liu K, Ralph W, Chen D, Qi M, Fan S, et al. Diindolylmethane alters gene expression in human keratinocytes in vitro. J. Nutr. 2002;132:3314–3324
  85. Sun S, Han J, Ralph WM, Chandrasekaran A, Liu K, Auborn KJ, et al. Endoplasmic reticulum stress as a correlate of cytotoxicity in human tumor cells exposed to diindolylmethane in vitro. Cell Stress Chaperones. 2004;9:76–87
  86. Marciniak SJ, Ron D. Endoplasmic reticulum stress signaling in disease. Physiol. Rev. 2006;86:1133–1149
  87. Barone MV, Crozat A, Tabaee A, Philipson L, Ron D. CHOP (GADD153) and its oncogenic variant, TLS-CHOP, have opposing effects on the induction of G1/S arrest. Genes Dev. 1994;8:453–464
  88. Jeon KI, Rih JK, Kim HJ, Lee YJ, Cho CH, Goldberg ID, et al. Pretreatment of indole-3-carbinol augments TRAIL-induced apoptosis in a prostate cancer cell line, LNCaP. FEBS Lett. 2003;544:246–251
  89. Fan S, Meng Q, Auborn K, Carter T, Rosen EM. BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells. Br. J. Cancer. 2006;94:407–426
  90. Scully R. Role of BRCA gene dysfunction in breast and ovarian cancer predisposition. Breast Cancer Res. 2000;2:324–330
  91. Tutt A, Ashworth A. The relationship between the roles of BRCA genes in DNA repair and cancer predisposition. Trends Mol. Med. 2002;8:571–576
  92. Meng Q, Goldberg ID, Rosen EM, Fan S. Inhibitory effects of Indole-3-carbinol on invasion and migration in human breast cancer cells. Breast Cancer Res. Treat. 2000;63:147–152
  93. Meng Q, Qi M, Chen DZ, Yuan R, Goldberg ID, Rosen EM, et al. Suppression of breast cancer invasion and migration by indole-3-carbinol: associated with up-regulation of BRCA1 and E-cadherin/catenin complexes. J. Mol. Med. 2000;78:155–165
  94. Rahman KM, Sarkar FH, Banerjee S, Wang Z, Liao DJ, Hong X, et al. Therapeutic intervention of experimental breast cancer bone metastasis by indole-3-carbinol in SCID-human mouse model. Mol. Cancer Ther. 2006;5:2747–2756
  95. Wu HT, Lin SH, Chen YH. Inhibition of cell proliferation and in vitro markers of angiogenesis by indole-3-carbinol, a major indole metabolite present in cruciferous vegetables. J. Agric. Food Chem. 2005;53:5164–5169
  96. Arora A, Seth K, Kalra N, Shukla Y. Modulation of P-glycoprotein-mediated multidrug resistance in K562 leukemic cells by indole-3-carbinol. Toxicol. Appl. Pharmacol. 2005;202:237–243
  97. Arora A, Shukla Y. Modulation of vinca-alkaloid induced P-glycoprotein expression by indole-3-carbinol. Cancer Lett. 2003;189:167–173
  98. Christensen JG, LeBlanc GA. Reversal of multidrug resistance in vivo by dietary administration of the phytochemical indole-3-carbinol. Cancer Res. 1996;56:574–581
  99. Chen D, Carter TH, Auborn KJ. Apoptosis in cervical cancer cells: implications for adjunct anti-estrogen therapy for cervical cancer. Anticancer Res. 2004;24:2649–2656
  100. Kim DS, Jeong YM, Moon SI, Kim SY, Kwon SB, Park ES, et al. Indole-3-carbinol enhances ultraviolet B-induced apoptosis by sensitizing human melanoma cells. Cell. Mol. Life Sci. 2006;63:2661–2668
  101. McGuire KP, Ngoubilly N, Neavyn M, Lanza-Jacoby S. 3,3′-Diindolylmethane and paclitaxel act synergistically to promote apoptosis in HER2/Neu human breast cancer cells. J. Surg. Res. 2006;132:208–213
  102. McDougal A, Gupta MS, Morrow D, Ramamoorthy K, Lee JE, Safe SH. Methyl-substituted diindolylmethanes as inhibitors of estrogen-induced growth of T47D cells and mammary tumors in rats. Breast Cancer Res. Treat. 2001;66:147–157
  103. Vanderlaag K, Samudio I, Burghardt R, Barhoumi R, Safe S. Inhibition of breast cancer cell growth and induction of cell death by 1,1-bis(3′-indolyl)methane (DIM) and 5,5′-dibromoDIM. Cancer Lett. 2006;236:198–212
  104. Chao WR, Yean D, Amin K, Green C, Jong L. Computer-aided rational drug design: a novel agent (SR13668) designed to mimic the unique anticancer mechanisms of dietary indole-3-carbinol to block Akt signaling. J. Med. Chem. 2007;50:3412–3415
  105. Kassouf W, Chintharlapalli S, Abdelrahim M, Nelkin G, Safe S, Kamat AM. Inhibition of bladder tumor growth by 1,1-bis(3′-indolyl)-1-(p-substitutedphenyl)methanes: a new class of peroxisome proliferator-activated receptor gamma agonists. Cancer Res. 2006;66:412–418
  106. Qin C, Morrow D, Stewart J, Spencer K, Porter W, Smith R, et al. A new class of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists that inhibit growth of breast cancer cells: 1,1-bis(3′-indolyl)-1-(p-substituted phenyl)methanes. Mol. Cancer Ther. 2004;3:247–260
  107. Chintharlapalli S, Burghardt R, Papineni S, Ramaiah S, Yoon K, Safe S. Activation of Nur77 by selected 1,1-bis(3′-indolyl)-1-(p-substituted phenyl)methanes induces apoptosis through nuclear pathways. J. Biol. Chem. 2005;280:24903–24914
  108. Cho SD, Yoon K, Chintharlapalli S, Abdelrahim M, Lei P, Hamilton S, et al. Nur77 agonists induce proapoptotic genes and responses in colon cancer cells through nuclear receptor-dependent and nuclear receptor-independent pathways. Cancer Res. 2007;67:674–683

PII: S0304-3835(08)00065-7

doi: 10.1016/j.canlet.2008.01.033

Cancer Letters
Volume 262, Issue 2 , Pages 153-163 , 18 April 2008

Article Tools

* Image Usage & Resolution