Modifying Effect of Indole-3-carbinol on Azoxymethane-induced Colon Carcinogenesis

  • Kang, Jin-Seok (Department of Biomedical Laboratory Science, Namseoul University)
  • Received : 2010.11.11
  • Accepted : 2010.12.26
  • Published : 2010.12.31

Abstract

Indole-3-carbinol (I3C), one of naturally occurring main components in cauliflower vegetables, is supposed to have a chemopreventive potential in experimental animals and humans. This study was investigated to examine chemopreventive effect of I3C on colon carcinogenesis induced by azoxymethane (AOM) using C57BL/6J mice. Mice were divided into three groups (10 or 9 mice/group). All mice were subcutaneously injected with AOM (5 mg/kg body weight, four times at weekly interval). After AOM treatment, animals of group 1 were fed by AIN-76A pellets as a basal diet. Animals of groups 2 and 3 were given I3C containing diets (100 and 300 ppm in diets, respectively) for 6 weeks until sacrifice. All mice were sacrificed at week 10 and the aberrant crypt foci (ACF) of the colonic mucosa were assessed after staining with methylene blue. Total numbers of ACF/colon in group 2 ($10.1{\pm}5.1$) or group 3 ($10.6{\pm}5.3$) were decreased compared to the values of group 1 ($14.4{\pm}10.2$). Among numbers of ACF formation, 5, 7, 8 and 10 ACF in group 2 and 3 were greatly different those of group 1. Total numbers of aberrant crypts (AC)/colon of group 2 ($20.1{\pm}10.1$) or group 3 ($22.0{\pm}10.9$) were decreased compared to the value of group 1 ($33.7{\pm}24.7$). Taken together, it suggests that I3C treatment may retard mouse colon carcinogenesis even after administration of AOM.

Keywords

References

  1. Bird RP, Good CK. The significance of aberrant crypt foci in understanding the pathogenesis of colon cancer. Toxicol Lett. 2000.112-113:395-402. https://doi.org/10.1016/S0378-4274(99)00261-1
  2. 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 U SA. 1991. 88: 9543-9547. https://doi.org/10.1073/pnas.88.21.9543
  3. Bonnesen C, Eggleston IM, Hayes JD. Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA damage in human colon cell lines. Cancer Res. 2001. 61: 6120-6130.
  4. Broadbent TA, Broadbent HS. 1 - 1. The chemistry and pharmacology of indole-3-carbinol (indole-3-methanol) and 3- (methoxymethyl)indole. [part I]. Curr Med Chem. 1998. 5: 337-352.
  5. Cover CM, Hsieh SJ, Cram EJ, Hong C, Riby JE, Bjeldanes LF, Firestone GL. Indole-3-carbinol and tamoxifen cooperate to arrest the cell cycle of MCF-7 human breast cancer cells. Cancer Res. 1999.59: 1244-1251.
  6. Cover CM, Hsieh SJ, Tran SH, Hallden G, Kim GS, Bjeldanes LF, Firestone GL. 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. https://doi.org/10.1074/jbc.273.7.3838
  7. Dashwood RH. Indole-3-carbinol: anticarcinogen or tumor promoter in brassica vegetables? Chem Biol Interact. 1998. 110: 1-5. https://doi.org/10.1016/S0009-2797(97)00115-4
  8. Dashwood RH, Arbogast DN, Fong AT, Pereira C, Hendricks JD, Bailey GS. Quantitative inter-relationships between aflatoxin B1 carcinogen dose, indole-3-carbinol anti-carcinogen dose, target . organ DNA adduction and final tumor response. Carcinogenesis 1989.10: 175-181. https://doi.org/10.1093/carcin/10.1.175
  9. Fenoglio-Preiser CM, Noffsinger A. Aberrant crypt foci: A review. Toxicol Pathol. 1999.27: 632-642. https://doi.org/10.1177/019262339902700604
  10. Grubbs CJ, Steele VE, Casebolt T, Juliana MM, Eto I, Whitaker LM, Dragnev KH, Kelloff GJ, Lubet RL. Chemoprevention of chemically-induced mammary carcinogenesis by indolc-3-carbinol. Anticancer Res. 1995. 15: 709-716.
  11. Guo D, Schut HA, Davis CD, Snyderwine EG, Bailey GS, Dashwood RH. Protection by chlorophyllin and indolc-3- carbinol against 2-amino-l-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP)-induced DNA adducts and colonic aberrant crypts in the F344 rat. Carcinogenesis 1995. 16: 2931-2937. https://doi.org/10.1093/carcin/16.12.2931
  12. Jellinck PH, Forkert PG, Riddick DS, Okey AB, Michnovicz JJ, Bradlow HL. Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation. Biochem Pharmacol. 1993.45: 1129-1136. https://doi.org/10.1016/0006-2952(93)90258-X
  13. Kang JS, Kim DJ, Ahn B, Nam KT, Kim KS, Choi M, Jang DD. Pre-initiation treatment of indole-3-carbinol (BC) inhibits 7,12-dimethylbenz[$\alpha$]anthracene (DMBA)-induced rat mammary carcinogenesis. Korean J Vet Res. 2001. 41: 549-555.
  14. Kang JS, Kim DJ, Ahn B, Nam KT, Kim KS, Choi M, Jang DD. Post-initiation treatment of Indole-3-carbinol did not suppress N-methyl-N-nitrosourea induced mammary carcinogenesis in rats. Cancer Lett. 2001. 169: 147-154. https://doi.org/10.1016/S0304-3835(01)00551-1
  15. Kang JS, Kim DJ, Jang DD. The modifying effect of indole- 3-carbinol (BC) and its metabolites, phytochemicals from Cruciferae vegetables, in chemical carcinogenesis and cancer prevention. J of Korean Association of Cancer Prevention 2000. 5: 199-208.
  16. Kelloff GJ, Crowell JA, Steele VE, Lubet RA, Malone WA, Boone CW, Kopelovich L, Hawk ET, Lieberman R. Lawrence JA, Ali I, Viner JL, Sigman CC. Progress in cancer chemo-prevention: development of diet-derived chemopreventive agents. J Nutr. 2000. 130: 467S-471S.
  17. Kim DJ, Han BS, Ahn B, Hasegawa R. Shirai T, Ito N, Tsuda H. Enhancement by indole-3-carbinol of liver and thyroid gland neoplastic development in a rat medium-term multiorgan carcinogenesis model. Carcinogenesis 1997. 18: 377-381. https://doi.org/10.1093/carcin/18.2.377
  18. Kim DJ, Lee KK, Han BS, Ahn B, Bae JH, Jang JJ. Biphasic modifying effect of indole-3-carbinol on diethylnitrosamine-induced preneoplastic glutathione S-transferase placental form-positive liver cell foci in Sprague-Dawley rats. Jpn J Cancer Res. 1994. 85: 578-583. https://doi.org/10.1111/j.1349-7006.1994.tb02399.x
  19. Kim DJ, Shin DH, Ahn B, Kang JS, Nam KT, Park CB, Kim CK, Hong JT, Kim YB, Yun YW, Jang DD, Yang KH. Chemo-prevention of colon cancer by Korean food plant components. Mutat Res. 2003. 523-524: 99-107. https://doi.org/10.1016/S0027-5107(02)00325-1
  20. 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.
  21. Kronbak R, Duus F, Vang O. Effect of 4-methoxyindole-3-carbinol on the proliferation of colon cancer cells in vitro, when treated alone or in combination with indole-3-carbinol. J Agric Food Chem. 2010. 58: 8453-8459. https://doi.org/10.1021/jf101806t
  22. Nakamura Y, Yogosawa S, Izutani Y, Watanabe H, Otsuji E, Sakai T. A combination of indol-3-carbinol and genistein synergistically induces apoptosis in human colon cancer HT-29 cells by inhibiting Akt phosphorylation and progression of autophagy. Mol Cancer. 2009.8: 100. https://doi.org/10.1186/1476-4598-8-100
  23. Nguyen HH, Aronchik I, Brar GA, Nguyen DH, Bjeldanes LF, Firestone GL. The dietary phytochemical indole-3-carbinol is a natural elastase enzymatic inhibitor that disrupts cyclin E protein processing. Proc Natl Acad Sci USA. 2008. 105: 19750-19755. https://doi.org/10.1073/pnas.0806581105
  24. Oganesian A, Hendricks JD, Pereira CB, Orner GA, Bailey GS, Williams DE. Potency of dietary indole-3-carbinol as a promoter of aflatoxin $B_1$-initiated hepatocarcinogenesis: results from a 9000 animal tumor study. Carcinogenesis 1999. 20: 453-458. https://doi.org/10.1093/carcin/20.3.453
  25. Papanikolaou A, Wang QS, Delker DA, Rosenberg DW. Azoxymethane-induced colon tumors and aberrant crypt foci in mice of different genetic susceptibility. Cancer Lett. 1998. 130: 29-34. https://doi.org/10.1016/S0304-3835(98)00101-3
  26. Paulsen JE, Steffensen IL, Loberg EM, Husoy T, Namork E, Alexander J. Qualitative and quantitative relationship between dysplastic aberrant crypt foci and tumorigenesis in the Min/+ mouse colon. Cancer Res. 2001. 61: 5010-5015.
  27. Pence BC, Buddingh F, Yang SP. Multiple dietary factors in the enhancement of dimethylhydrazine carcinogenesis: main effect of indole-3-carbinol. J Natl Cancer Inst. 1986. 77: 269-276.
  28. Shoemaker AR, Moser AR, Dove WF. N-ethyl-N-nitrosourea treatment of multiple intestinal neoplasia (Min) mice: age-related effects on the formation of intestinal adenomas, cystic crypts, and epidermoid cysts. Cancer Res. 1995. 55: 4479-4485.
  29. Steinmetz KA, Potter JD. Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc. 1996. 96: 1027-1039. https://doi.org/10.1016/S0002-8223(96)00273-8
  30. Takahashi M, Fukuda K, Sugimura T, Wakabayashi K. Betacatenin is frequently mutated and demonstrates altered cellular location in azoxymethane-induced rat colon tumors. Cancer Res. 1998.58: 42-46.
  31. Wang QS, Papanikolaou A, Sabourin CL, Rosenberg DW. Altered expression of cyclin D1 and cyclin-dependent kinase 4 in azoxymethane-induced mouse colon tumorigenesis. Carcinogenesis 1998.19: 2001-2006. https://doi.org/10.1093/carcin/19.11.2001
  32. Wargovich MJ, Chen CD, Jimenez A, Steele VE, Velasco M, Stephens LC, Price R, Gray K, Kelloff GJ. Aberrant crypts as a biomarker for colon cancer: evaluation of potential chemopreventive agents in the rat. Cancer Epidemiol Biomarkers Prev. 1996. 5: 355-360.
  33. Whiteley LO, Hudson L, Jr., Pretlow TP. Aberrant crypt foci in the colonic mucosa of rats treated with a genotoxic and nongenotoxic colon carcinogen. Toxicol Pathol. 1996. 24: 681-689. https://doi.org/10.1177/019262339602400602