MECHANIZM DZIAŁANIA INDOLO-3-KARBINOLU I 3,3´-DIINDOLILOMETANU W CHEMOPREWENCJI CHORÓB NOWOTWOROWYCH

Teresa Żołek; Aleksandra Trzeciak

doi:10.56782/pps.71

Published : 2017-03-29

Vol. 15 No. 2 (2017)

THE MECHANISM OF ACTION OF INDOLE-3-CARBINOL AND 3,3´-DIINDOLYLMETHANE IN CANCER CHEMOPREVENTION

Teresa Żołek

Aleksandra Trzeciak

DOI: https://doi.org/10.56782/pps.71

Abstract

Indole derivatives are aromatic heterocyclic organic compounds important in the development of new pharmaceuticals. Indole-3-carbinole (I3C) and 3,3´-diindolylmethane (DIM) occur naturally in cruciferous plants, but their derivatives can be also obtained synthetically. In vitro studies indicate that I3C and DIM inhibit cancer cell proliferation at the G1 phase and induce their apoptosis. It has been demonstrated that they alter estrogen metabolism. Microarray gene expression profiling indicates that indole derivatives affect the expression of multiple genes that are involved in the control of the cell cycle, apoptosis, signal transduction, angiogenesis, and cell invasion. It was found that in animal models indole derivatives prevent the onset of breast and cervical cancer. In phase II and phase III clinical trials, I3C and DIM have been identified as a potential chemopreventive agents against human breast and ovarian cancer, and vulvar intraepithelial neoplasia. The precise molecular mechanism, by which indole derivatives exert their tumor suppressive effects is still under study. I3C and DIM are components of dietary supplements recommended in cancer prevention.

Keywords:

indole-3-carbinol, 3,3´-diindolylmethane, chemoprevention, cervical cancer, breast cancer, Brassicaceae plants

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Żołek, T., & Trzeciak, A. (2017). THE MECHANISM OF ACTION OF INDOLE-3-CARBINOL AND 3,3´-DIINDOLYLMETHANE IN CANCER CHEMOPREVENTION. Prospects in Pharmaceutical Sciences, 15(2), 8–15. https://doi.org/10.56782/pps.71

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References

Stewart BW, Wild CP, International Agency for Research on Cancer, WHO. World Cancer Report 2014.

Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin A.A, Kim S, Wilson CJ, Lehar J, Kryukov GV, Sonkin D, Reddy A, Liu M, Murray L, Berger MF, Monahan JE, Morais P, Meltzer J, Korejwa A, Jane´-Valbuena J, Mapa FA, Thibault J, Bric-Furlong E, Raman P, Shipway A, Engels IH, Cheng J, Yu KG, Yu J, Aspesi P, de Silva M, Jagtap K, Jones MD, Wang L, Hatton C, Palescandolo E, Gupta S, Mahan S, Sougnez C, Onofrio RC, Liefeld T, MacConaill L, Winckler W, Reich M, Li N, Mesirov JP, Stacey B, Gad G, Ardlie K, Chan V, Myer VE, Weber BL, Porter J, Warmuth M, Finan P, Harris LJ, Meyerson M, Golub TR, Morrissey MP, Sellers WR, Schlegel R, Garraway LA, The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 2012, 483, 603-607. DOI: https://doi.org/10.1038/nature11003

Landis-Piwowar KR, Iyer NR, Cancer Chemoprevention: Current State of the Art. Cancer Growth Metastasis. 2014, 7, 19-25. DOI: https://doi.org/10.4137/CGM.S11288

Maru GB, Hudlikar RR, Kumar G, Gandhi K, Mahimkar MB, Understanding the molecular mechanisms of cancer prevention by dietary phytochemicals: From experimental models to clinical trials. World J. Biol. Chem. 2016, 7 (1), 88-89. DOI: https://doi.org/10.4331/wjbc.v7.i1.88

Kotecha R, Takami A, Espinoza JL, Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence. Oncotarget 2016, 7, No.32, 52517-52529. DOI: https://doi.org/10.18632/oncotarget.9593

Drvesh AS, Bishave A, Chemopreventive and therapeutic potential of tea polyphenols in hepatocellular cancer. Nutr Cancer 2013, 65(3), 329-344. DOI: https://doi.org/10.1080/01635581.2013.767367

Higdon JV, Delage B, Williams DV, Dashwood RH, Cruciferous Vegetables and Human Cancer Risk: Epidemiologic Evidence and Mechanistic Basis. Pharmacol Res. 2007, 55(3), 224-236. DOI: https://doi.org/10.1016/j.phrs.2007.01.009

Lynn A, Collins A, Fuller Z, Hillman K, Ratcliffe B, Cruciferous vegetables and colo-rectal cancer. Proc Nutr Soc 2006, 65(1), 135-144. DOI: https://doi.org/10.1079/PNS2005486

Wu Q J, Yang Y, Wang J, Li HH, Xiang YB, Cruciferous vegetable consumption and gastric cancer risk: A meta-analysis of epidemiological studies. Cancer Sci 2013, 104, 1067-1073. DOI: https://doi.org/10.1111/cas.12195

Lopezotin C, Diamandis EP, Breast and Prostate Cancer: An Analysis of Common Epidemiological, Genetic, and Biochemical Features. Endocrine Reviews 1998, 19(4), 365-396. DOI: https://doi.org/10.1210/edrv.19.4.0337

Jung S, Spiegelman D, Baglietto L, Bernstein L, Boggs DA, Van den Brandt PA, Buring JE, Cerhan JR, Gaudet MM, Giles GG, Goodman G, Hakansson N, Hankinson SE, Helzlsouer K, Horn-Ross PL, Inoue M, Krogh V, Lof M, McCullough ML, Miller AB, Neuhouser ML, Palmer JR, Park Y, Robien K, Rohan TE, Scarmo S, Schairer C, Schouteneo LJ, Shikany JM, Sieri S, Tsugane S, Visvanathan K, Weiderpass E, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Zhang SM, Zhang X, Ziegler RG, Smith-Warner SA, Fruit and Vegetable Intake and Risk of Breast Cancer by Hormone Receptor Status. JNCI 2013, 105, 219-236. DOI: https://doi.org/10.1093/jnci/djs635

Kolonel N, Hankin JH, Wilkens LR, Fukunaga FH, Hinds MW, An epidemiologic study of thyroid cancer in Hawaii. Cancer Causes Control 1990, 1, 223-234. DOI: https://doi.org/10.1007/BF00117474

Schiffman MH, Pickle LW, Fontham E, Zahm SH, Falk R, Mele J, Correa P, Fraumeni JFJ, Case-control study of diet and mesothelioma in Louisiana. Cancer Res. 1988, 48(10), 2911-2915.

Auborn KJ, Can Indole-3-Carbinol–Induced Changes in Cervical Intraepithelial Neoplasia Be Extrapolated to Other Food Components? J Nutr 2006, 136, 26765-26785. DOI: https://doi.org/10.1093/jn/136.10.2676S

Dashwood RH, Indole-3-carbinol: Anticarcinogen or tumor promoter in brassica vegetables? Chemico-Biological Interactions 1998, 110, 1-5.

Rahman WKM, Sarkar FH, Banerjee S, Wang Z, Liao DJ, Hong X, Sarkar N. H., Therapeutic intervention of experimental breast cancer bone metastasis by indole-3-carbinol in SCID-human mouse model. Mol Cancer Ther 2006, 5(11), 2747-2756. DOI: https://doi.org/10.1158/1535-7163.MCT-06-0221

Le Marchand L, Hankin JH, Kolonel LN, Wilkens LR, Vegetables and fruit consumption in relation to prostate cancer risk in Hawaii: a revaluation of the effect of dietary beta-carotene. Am J Epidemiol. 1991, 133, 215-219. DOI: https://doi.org/10.1093/oxfordjournals.aje.a115865

Keck A, Finley JW, Cruciferous vegetables: cancer protective mechanisms of glucosinolate hydrolysis products and selenium. Int Cancer Ther 2004, 3(1), 5 -12. DOI: https://doi.org/10.1177/1534735403261831

Angelino D, Jeffery E, Glucosinolate hydrolysis and bioavailability of resulting isothiocyanates: Focus on glucoraphanin. J Fun Foods 2014, 7, 67-76. DOI: https://doi.org/10.1016/j.jff.2013.09.029

Grose KR., Bjeldanes LF, Oligomerization of indole-3-carbinol in aqueous acid. Chem Res Toxicol 1992, 5, 188-193.

Anderton MJ, Jukes R, Lamb J, Manson MM, Gescher A, Steward WP, Williams ML, Liquid chromatographic assay for the simultaneous determination of indole-3-carbinol and its acid condensation products in plasma. J Chrom. B, 2003, 787, 281-291. DOI: https://doi.org/10.1016/S1570-0232(02)00923-6

Aggarwal BB., Ichikawa H, Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle 2005, 4(9), 1201-1215. DOI: https://doi.org/10.4161/cc.4.9.1993

Grose KR, Bjeldanes LF, Oligomerysation of indole-3-carbinol in aqueous acid. Chem Res Toxicol 1992, 5, 188-193. DOI: https://doi.org/10.1021/tx00026a007

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 Metabol Disposit 1995, 23 (9), 965-975.

Hrncirik K, Valusek J, Valisek J, Investigation of ascorbigen as a breakdown product of glucobrassicin autolysis in Brassica vegetables. Eur Food Res Technol 2001, 212, 576 - 581. DOI: https://doi.org/10.1007/s002170100291

Buskov S, Hansen LB, Olsen CE, Sorensen JC, Sorensen H, Determination of ascorbigens in autolysates of various brassica species using supercritical fluid chromatography. J Agr Food Chem 2000, 48 (7), 2693-2701. DOI: https://doi.org/10.1021/jf000165r

Sepkovic DW, Bradlow HL, Ball M, Quantitative determination of 3,3'-diindolylmethane in urine of individuals receiving indole-3-carbinol. Nutr Cancer 2001, 41, 57-63. DOI: https://doi.org/10.1207/S15327914NC41-1&2_7

Weng JR, Tsai CH, Kulp SK, Chen CS, Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer Lett 2008, 262, 153-163. DOI: https://doi.org/10.1016/j.canlet.2008.01.033

Aubom KJ, Fan S, Rosen EM, Goodwin L, Chandraskaren A, Williams DE, Chen D, Carter TH, Indole-3-Carbinol Is a Negative Regulator of Estrogen. J Nutr 2003, 133, 24705-24755. DOI: https://doi.org/10.1093/jn/133.7.2470S

Maliszewska M, Kurkumina, indolo-3-karbinol i resweratrol w chemoprewencji raka sutka. Postępy Fitoterapii 2013, 1, 28-35.

Szwejda-Grzybowska J, Antykancerogenne składniki warzyw kapustnych i ich znaczenie w profilaktyce chorób nowotworowych. Bromat. Chem. Toksykol. 2011, XLIV, 4 1039-1046.

Dżugan M, Znaczenie warzyw kapustnych w profilaktyce nowotworów. Zdrowie Publiczne 2007, 117 (3), 397-401.

www.globocan.iarc.fr/Pages/fact_sheets_cancer.aspx

Suto A, Bradlow HL, Wong GY, Osborne MP, Telang NT, Persistent estrogen responsiveness of ras oncogene-transformed mouse mammary epithelial cells. Steroids 1992, 57, 262-268. DOI: https://doi.org/10.1016/0039-128X(92)90058-H

Bradlow HL, Hershoop RJ, Martucci CP, Fishman J, Estradiol 16 alpha-hydroxylation in the mouse correlates with mammary tumor incidence and presence of murine mammary tumor virus: a possible model for the hormonal etiology of breast cancer in humans. Proc Natl Acad Sci USA 1985, 82(18), 6295-6299. DOI: https://doi.org/10.1073/pnas.82.18.6295

Bradlow HL, Hershcopf R, Martucci C, Fiszman J, 16α-Hydroxylation of Estradiol: A Possible Risk Marker for Breast Cancer. Annals of the New York Academy of Sciences 1986, 464, 138-151. DOI: https://doi.org/10.1111/j.1749-6632.1986.tb16001.x

Emaus MJ, Peeters PH, Bakker MF, Overvad K, Tjønneland A, Olsen A, Romieu I, Ferrari P, Dossus L, Boutron-Ruault MC, Baglietto L, Fortner RT, Kaaks R, Boeing H, Trichopoulou A, Lagiou P, Trichopoulos D, Masala G, Pala V, Panico S, Tumino R, Polidoro S, Skeie G, Lund E, Weiderpass E, Quirós JR, Travier N, Sánchez MJ, Chirlaque MD, Ardanaz E, Dorronsoro M, Winkvist A, Wennberg M, Bueno de Mesquita HB, Khaw KT, Travis RC, Key TJ, Aune D, Gunter M, Riboli E, Van Gils CH, Vegetable and fruit consumption and the risk of hormone receptor–defined breast cancer in the EPIC cohort. Am J Clin Nutr 2016, 103, 168-177. DOI: https://doi.org/10.3945/ajcn.114.101436

Parkin DR, Malejka-Giganti D, Differences in the hepatic P-450-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. DOI: https://doi.org/10.1016/j.cdp.2003.11.006

Jin L, Qi M, Chen DZ, Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice. Cancer Res 1999, 59, 3991-3997.

Wang TT, Milner MJ, Milner JA, Kim YS, Estrogen receptor alpha as a target for indole-3-carbinol. Journal of Nutr. Biochem. 2006, 17, 659-664. DOI: https://doi.org/10.1016/j.jnutbio.2005.10.012

Brandi G, Paiardini M, Cervasi B, Fiorucci C, Filippone P, Marco C, Zaffaroni N, Magnani M, 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.

Das SK, Hashimoto T, Shimizu K, Yoshida T, Sakai T, Sowa Y, Komoto A, Kanazawa K, Fucoxanthin induces cell cycle arrest at G0/G1 phase in human colon carcinoma cells through up-regulation of p21WAF1/Cip1. Bioch Biophys Acta 2005, 1726, 328-335. DOI: https://doi.org/10.1016/j.bbagen.2005.09.007

Cram EJ, Liu BD, Bjeldanes LF, Firestone GL, Indole-3-carbinol inhibits CDK6 expression in human NCF-7 breast cancer cell by disrupting Sp1 transcription factor interactions with a composite element in the CDK6 gene promoter. J Biol Chem 2001, 276, 22332-22340. DOI: https://doi.org/10.1074/jbc.M010539200

Vousden KH, Lu X, Live or let die: the cell’s response to p53. Nat. Rev. Cancer, 2002, 2, 594-604. DOI: https://doi.org/10.1038/nrc864

Marconett CN, Singhal AK, Sundar SN, Firestone GL, Indole-3carbinol disrupts estrogen receptor-alpha dependent expression of insulin-like growth factor-1 receptor and insulin receptor substrate-1 and proliferation of human breast cancer cells. Mol Cell Endocrinol 2012, 363, 74-84. DOI: https://doi.org/10.1016/j.mce.2012.07.008

Brew CT, Aronchik I, Hsu JC, Sheen JH, Dickson RB, Bjeldanes LF, Firestone GL, Indole-3-carbinol activates the ATM signaling pathway independent of DNA damage to stabilize p53 and induce G1 arrest of human mammary epithelial cells. Int J Cancer 2006, 118, 857-868. DOI: https://doi.org/10.1002/ijc.21445

Brew CT, Aronchik I, Kosco K, McCammon J, Bjeldanes LF, Firestone GL, Indole-3-carbinol inhibits MDA-MB-231 breast cancer cell motility and induces stress fibers and focal adhesion formation by activation of Rh kinase activity. Int J Cancer 2009, 124, 2294-2302. DOI: https://doi.org/10.1002/ijc.24210

Rahman KM, Aranha O, Sarkar FM, Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in nontumorigenic breast epithelial cells. Nutr Cancer 2003, 45, 101-112. DOI: https://doi.org/10.1207/S15327914NC4501_12

Rahman KM, Sarkar FM, 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. DOI: https://doi.org/10.1158/0008-5472.364.65.1

Rajoria S, Suriano R, Wilson YL, Schantz SP, Moscatello A, Geliebter J, Tiwari R K, 3,3'-diindolylmethane inhibits migration and invasion of human cancer cells through combined suppression of ERK and AKT pathways. Oncol Reports 2011, 25(2), 491- 497. DOI: https://doi.org/10.3892/or.2010.1076

Ahmad A, Biersack B, Li Y, Kong D, Bao B, Schobert RB, Padhye SH, Sarkar F, Targeted Regulation of PI3K/Akt/mTOR/NF-κB Signaling by Indole Compounds and their Derivatives: Mechanistic Details and Biological Implications for Cancer Therapy. Curr. Med. Chem. 2013, 13, 1002-1013. DOI: https://doi.org/10.2174/18715206113139990078

Ławicki S, Zajkowska M, Głażewska EK, Będkowska GE, Szmitkowski M, Plasma levels and diagnostic utility of VEGF, MMP-9, and TIMP-1 in the diagnosis of patients with breast cancer. Oncology Targets Therapy 2016, 9, 911-919. DOI: https://doi.org/10.2147/OTT.S99959

Moiseeva EP, Heukers R, Manson MM, EGFR and Src are involved in indole-3-carbinol-induced death and cell cycle arrest of human breast cancer cells. Carcinogenesis 2006, 28, 435-445. DOI: https://doi.org/10.1093/carcin/bgl171

Bresnick E, Birt DF, Wolterman K, Wheeler M, Markin RS, Reduction in mammary tumorigenesis in the rat by cabbage and cabbage residue. Carcinogenesis 1990, 11 (7), 1159-1163. DOI: https://doi.org/10.1093/carcin/11.7.1159

Lubet RA, Heckman BM, De Flora SL, Steele VE, Crowell JA, Juliana MM, Grubbs CJ, Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and diindolylmethane (DIM) on chemically-induced mammary carcinogenesis: is DIM a substitute for I3C? Oncology Reports 2011, 26 (3), 731-736. DOI: https://doi.org/10.3892/or.2011.1316

Nquyen HH, Lavrenov SN, Sundar SN, Nquyen DH, Tseng M, Marconett CN, Kung J, Staub RE, Preobrazhenskaya MN, Bieldanes LF, Firestone GL, 1-Benzyl-indole-3-carbinol is a novel indole-3-carbinol derivative with significantly enhanced potency of anti-proliferative and anti-estrogenic properties in human breast cancer cells. Chem Biol Interact 2010, 186 (3), 255-266. DOI: https://doi.org/10.1016/j.cbi.2010.05.015

Wang ML, Lin SH, Hou YY, Chen YH, Suppression of Lipid Accumulation by Indole-3-Carbinol Is Associated with Increased Expression of the Aryl Hydrocarbon Receptor and CYP1B1 Proteins in Adipocytes and with Decreased Adipocyte-Stimulated Endothelial Tube Formation. Int J Mol Sci 2016, 17 (8), 1256-1267. DOI: https://doi.org/10.3390/ijms17081256

Rose P, Huang Q, Ong CN, Whiteman M, Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells. Toxicol Applied Pharmacol 2005, 209, 105-113. DOI: https://doi.org/10.1016/j.taap.2005.04.010

Bosch FX, de Sanjosé S, Chapter 1: Human papillomavirus and cervical cancer-burden and assessment of causality. J Natl Cancer Inst Monogr. 2003, 31, 3-13. DOI: https://doi.org/10.1093/oxfordjournals.jncimonographs.a003479

Byers T, Nishikawa A, Manson M, Seow A, Hecht S, Dragsted L, Stoner G, Agudo A, Bradlow L, Zhang Y, Chung FL, Taioli E, Thornalley J, Johnson I, Vang O, Kassie F, Schut H, Bailey G, Hayes J, Loft S, Mithen R, Miller A, Cruciferous vegetables, Isothiocyanates and Indoles. Handbook of Cancer Prevention, IARC Press, Lyon 2004, 9.

Carter TH, Liu K, Ralph WJ, Chen D, Qi M, Fan S, Yuan F, Rosen EM, Auborn KJ, Diindolylmethane Alters Gene Expression in Human Keratinocytes In Vitro. J. Nutr. 2002, 132, 3314-3324.

Carter TH, Liu K, Ralph WJ, Chen D, Qi M, Fan S, Yuan F, Rosen EM, Auborn KJ, Diindolylmethane alters gene expression in human keratinocytes in vitro. J Nutr 2002, 132(11), 3314-3324. DOI: https://doi.org/10.1093/jn/132.11.3314

Meng Q, Yuan F, Goldberg ID, Rosen EM, Auborn K, Fan S, Indole-3-carbinol is a negative regulator of estrogen receptor-alpha signaling in human tumor cells. J. Nutr. 2000, 130, 2927-2931. DOI: https://doi.org/10.1093/jn/130.12.2927

Sepkovic DW, Pagan DV, Stein J, Carlisle AD, Ksieski HB, Auborn K, Nyirenda T, Bradlow HL, Evaluation of 3,3’-Diindolylmethane with Gardasil Quadrivalent HPV Vaccine in K14-HPV16 -Transgenic Mice Cervical Histology. In Vivo 2013, 27, 299- 304.

Arbeit JM, Howley PM, Hanahan D, Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice. Proc Natl Acad Sci USA 1996, 93, 2930-2935. DOI: https://doi.org/10.1073/pnas.93.7.2930

Jin L, Qi M, Chen DZ, Anderson A, Yang GY, Arbeit JM, Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice. Cancer Res. 1999, 59, 3991-3997.

Bell MC, Crowlay-Nowick P, Bradlow HL, Sepkovic DW, Schmidt-Grimmingen D, Howell P, Mayeaux EJ, Tucker A, Turbat-Herrera EA, Mathis JM, Placebo-Controlled Trial of Indole-3-Carbinol in the Treatment of CIN. Gynecologic Oncology 2000, 78, 123-129. DOI: https://doi.org/10.1006/gyno.2000.5847

Dashwood RH, Indole–3–carbinol: anticarcinogen or tumor promoter in Brassica vegetables? Chem Biol Interact 1998, 110, 1-5. DOI: https://doi.org/10.1016/S0009-2797(97)00115-4

https://clinicaltrials.gov/ct2/show/study/NCT01391689, 2016

Teresa Żołek

tzolek@wum.edu.pl

Affiliation:

Zakład Chemii Organicznej, Wydział Farmaceutyczny z Oddziałem Medycyny Laboratoryjnej, Warszawski Uniwersytet Medyczny, ul. Banacha 1, 02-097 Warszawa Poland