DIM (Diindolylmethaan)
- DIM (Diindolylmethaan) is een metaboliet van indool-3-carbinol, wat voorkomt in kruisbloemige groenten
- DIM wordt gevormd in de darmen na vertering van indool-3-carbinol
- Onderzoeken wijzen op ontstekingsremmende effecten en oestrogeenverlagende effecten bij kanker.
- Diindolylmethaan gebruikt men het meest in doses van 100-150 mg per dag gedurende 1-12 maanden.
- DIM gebruikt men oraal bij oestrogeendominantie, premenstrueel syndroom (PMS) en gewichtsverlies.
In het kort
- DIM (Diindolylmethaan) is een metaboliet van indool-3-carbinol, wat voorkomt in kruisbloemige groenten
- DIM wordt gevormd in de darmen na vertering van indool-3-carbinol
- Onderzoeken wijzen op ontstekingsremmende effecten en oestrogeenverlagende effecten bij kanker.
- Diindolylmethaan gebruikt men het meest in doses van 100-150 mg per dag gedurende 1-12 maanden.
- DIM gebruikt men oraal bij oestrogeendominantie, premenstrueel syndroom (PMS) en gewichtsverlies.
Wat is DIM (Diindolylmethaan)?
DIM, of de volledige naam Diindolylmethaan, is een belangrijke actieve metaboliet van indole-3-carbinol. Dit is een chemische stof die voorkomt in kruisbloemige groenten, waaronder broccoli, kool, bloemkool, boerenkool en spruitjes. DIM wordt gevormd in de darmen na vertering van indool-3-carbinol1,2,3,4.
In maagzuur is indol-3-carbinol onstabiel en wordt het gemakkelijk omgezet in een verscheidenheid aan verbindingen, waaronder diindolylmethaan5. Een typisch dieet levert 20-120 mg indol-3-carbinol per dag op. Ongeveer 10% tot 20% wordt omgezet in diindolylmethaan, wat 2-24 mg per dag oplevert4,6,7.
Gebruik
Oraal
Diindolylmethaan gebruikt men oraal bij goedaardige prostaathypertrofie (BPH) en borst-, baarmoeder-, prostaat-, en colorectale kanker. Het wordt ook gebruikt voor het premenstrueel syndroom (PMS) en gewichtsverlies.
Veiligheid
Volwassenen
Waarschijnlijk veilig bij oraal gebruik in hoeveelheden die gewoonlijk in voedingsmiddelen worden aangetroffen. Het typische dieet levert dagelijks 2-24 mg diindolylmethaan54,60,61. Mogelijk veilig bij oraal gebruik en op de juiste manier in medicinale doses. Diindolylmethaan is met veiligheid gebruikt in doses tot 150 mg per dag gedurende maximaal 1 jaar56,57,58,59.
Kinderen
Waarschijnlijk veilig bij oraal gebruik in hoeveelheden die gewoonlijk in voedingsmiddelen worden aangetroffen. Het typische dieet levert dagelijks 2-24 mg diindolylmethaan54,61,62.
Zwangerschap en lactatie
Waarschijnlijk veilig bij oraal gebruik in hoeveelheden die gewoonlijk in voedingsmiddelen worden aangetroffen. Het typische dieet levert dagelijks 2-24 mg diindolylmethaan54,61,62. Er is onvoldoende betrouwbare informatie beschikbaar over de veiligheid van diindolylmethaan bij gebruik in grotere hoeveelheden dan in voedingsmiddelen tijdens zwangerschap en borstvoeding; vermijd te gebruiken.
Interacties
Medicijnen
Diindolylmethaan zou de serumspiegels van CYP1A2-substraten kunnen verlagen. In vitro bewijs suggereert dat diindolylmethaan CYP1A2 kan induceren63,64. Theoretisch zou DIM het metabolisme van CYP1A2-substraten kunnen verhogen en de serumconcentraties kunnen verlagen. Deze interactie is niet gemeld bij mensen.
Theoretisch zou diindolylmethaan het risico op hyponatriëmie kunnen verhogen bij gebruik met natriumafbrekende diuretica. Grote doses diindolylmethaan (600 mg per dag) zijn in klinisch onderzoek in verband gebracht met twee gevallen van asymptomatische hyponatriëmie65.
Theoretisch zou diindolylmethaan de effecten van oestrogenen kunnen versterken of verminderen. Diindolylmethaan kan milde oestrogene of anti-oestrogene effecten hebben54. Theoretisch kunnen grote hoeveelheden diindolylmethaan interfereren met hormoonvervangingstherapie.
Kruiden en supplementen
Geen bekend.
Voeding
Geen bekend.
Lab testen
Geen bekend.
Ziekten
Overleg met een behandelend arts is noodzakelijk wanneer patiënten door ziekte reguliere behandelingen ondergaan. Voorlopig onderzoek suggereert echter ook dat diindolylmethaan anti-oestrogene effecten zou kunnen hebben en mogelijk beschermend zou kunnen zijn tegen hormoonafhankelijke kankers54.
Dosering
Volwassen (oraal)
Diindolylmethaan gebruikt men het meest in doses van 100-150 mg per dag gedurende 1-12 maanden.
- Smith, T. K., Lund, E. K., Clarke, R. G., Bennett, R. N., & Johnson, I. T. (2005). Effects of Brussels sprout juice on the cell cycle and adhesion of human colorectal carcinoma cells (HT29) in vitro. Journal of Agricultural and Food chemistry, 53(10), 3895-3901.
- Del Priore, G., Gudipudi, D. K., Montemarano, N., Restivo, A. M., Malanowska-Stega, J., & Arslan, A. A. (2010). Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecologic oncology, 116(3), 464-467.
- Castanon, A., Tristram, A., Mesher, D., Powell, N., Beer, H., Ashman, S., … & Sasieni, P. (2012). Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. British journal of cancer, 106(1), 45-52.\
- Riby, J. E., Chang, G. H., Firestone, G. L., & Bjeldanes, L. F. (2000). Ligand-independent activation of estrogen receptor function by 3, 3′-diindolylmethane in human breast cancer cells. Biochemical pharmacology, 60(2), 167-177.
- Chen, I., Safe, S., & Bjeldanes, L. (1996). Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. Biochemical pharmacology, 51(8), 1069-1076.
- Olenina, L., Patel, I. P., & Portal, A. P. Health Information Indole-3-Carbinol.
- Ashrafian, L., Sukhikh, G., Kiselev, V., Paltsev, M., Drukh, V., Kuznetsov, I., … & Andrianova, E. (2015). Double-blind randomized placebo-controlled multicenter clinical trial (phase IIa) on diindolylmethane’s efficacy and safety in the treatment of CIN: implications for cervical cancer prevention. EPMA Journal, 6(1), 1-12.
- McDougal, A., Gupta, M. S., Ramamoorthy, K., Sun, G., & Safe, S. H. (2000). Inhibition of carcinogen-induced rat mammary tumor growth and other estrogen-dependent responses by symmetrical dihalo-substituted analogs of diindolylmethane. Cancer letters, 151(2), 169-179.
- Chen, I., McDougal, A., Wang, F., & Safe, S. (1998). Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Carcinogenesis, 19(9), 1631-1639.
- Ge, X., Yannai, S., Rennert, G., Gruener, N., & Fares, F. A. (1996). 3, 3′-Diindolylmethane induces apoptosis in human cancer cells. Biochemical and Biophysical Research Communications, 228(1), 153-158.
- Hong, C., Firestone, G. L., & Bjeldanes, L. F. (2002). Bcl-2 family-mediated apoptotic effects of 3, 3′-diindolylmethane (DIM) in human breast cancer cells. Biochemical pharmacology, 63(6), 1085-1097.
- Wang, T. T., Milner, M. J., Milner, J. A., & Kim, Y. S. (2006). Estrogen receptor α as a target for indole-3-carbinol. The Journal of nutritional biochemistry, 17(10), 659-664.
- Jin, Y., Zou, X., & Feng, X. (2010). 3, 3′-Diindolylmethane negatively regulates Cdc25A and induces a G2/M arrest by modulation of microRNA 21 in human breast cancer cells. Anti-cancer drugs, 21(9), 814-822.
- Chen, I., McDougal, A., Wang, F., & Safe, S. (1998). Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Carcinogenesis, 19(9), 1631-1639.
- Hong, C., Firestone, G. L., & Bjeldanes, L. F. (2002). Bcl-2 family-mediated apoptotic effects of 3, 3′-diindolylmethane (DIM) in human breast cancer cells. Biochemical pharmacology, 63(6), 1085-1097.
- Degner, S. C., Papoutsis, A. J., Selmin, O., & Romagnolo, D. F. (2009). Targeting of aryl hydrocarbon receptor-mediated activation of cyclooxygenase-2 expression by the indole-3-carbinol metabolite 3, 3′-diindolylmethane in breast cancer cells. The Journal of nutrition, 139(1), 26-32.
- Xue, L., Firestone, G. L., & Bjeldanes, L. F. (2005). DIM stimulates IFNγ gene expression in human breast cancer cells via the specific activation of JNK and p38 pathways. Oncogene, 24(14), 2343-2353.
- Hsu, E. L., Chen, N., Westbrook, A., Wang, F., Zhang, R., Taylor, R. T., & Hankinson, O. (2008). CXCR4 and CXCL12 down-regulation: a novel mechanism for the chemoprotection of 3, 3′-diindolylmethane for breast and ovarian cancers. Cancer letters, 265(1), 113-123.
- Kim, E. J., Shin, M., Park, H., Hong, J. E., Shin, H. K., Kim, J., … & Park, J. H. Y. (2009). Oral administration of 3, 3′-diindolylmethane inhibits lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice. The Journal of nutrition, 139(12), 2373-2379.
- Rahman, K. W., Ali, S., Aboukameel, A., Sarkar, S. H., Wang, Z., Philip, P. A., … & Raz, A. (2007). Inactivation of NF-κB by 3, 3′-diindolylmethane contributes to increased apoptosis induced by chemotherapeutic agent in breast cancer cells. Molecular cancer therapeutics, 6(10), 2757-2765.
- Kotsopoulos, J., Zhang, S., Akbari, M., Salmena, L., Llacuachaqui, M., Zeligs, M., … & Narod, S. A. (2014). BRCA1 mRNA levels following a 4–6-week intervention with oral 3, 3′-diindolylmethane. British journal of cancer, 111(7), 1269-1274.
- Bradlow, H. L., Sepkovic, D. W., Telang, N. T., & Osborne, M. P. (1999). Multifunctional aspects of the action of indole‐3‐carbinol as an antitumor agent. Annals of the New York Academy of Sciences, 889(1), 204-213.
- Leong, H., Firestone, G. L., & Bjeldanes, L. F. (2001). Cytostatic effects of 3, 3′-diindolylmethane in human endometrial cancer cells result from an estrogen receptor-mediated increase in transforming growth factor-αCarcinogenesis, 22(11), 1809-1817.
- Sepkovic, D. W., Bradlow, H. L., & Bell, M. (2001). Quantitative Determination of 3, 3?-Diindolylmethane inUrine of Individuals Receiving Indole-3-Carbinol. Nutrition and cancer, 41(1-2), 57-63.
- Tadi, K., Chang, Y., Ashok, B. T., Chen, Y., Moscatello, A., Schaefer, S. D., … & Tiwari, R. K. (2005). 3, 3′-Diindolylmethane, a cruciferous vegetable derived synthetic anti-proliferative compound in thyroid disease. Biochemical and biophysical research communications, 337(3), 1019-1025.
- Abdelrahim, M., Newman, K., Vanderlaag, K., Samudio, I., & Safe, S. (2006). 3, 3′-diindolylmethane (DIM) and its derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5. Carcinogenesis, 27(4), 717-728.
- Chen, Y., Xu, J., Jhala, N., Pawar, P., Zhu, Z. B., Ma, L., … & McDonald, J. M. (2006). Fas-mediated apoptosis in cholangiocarcinoma cells is enhanced by 3, 3′-diindolylmethane through inhibition of AKT signaling and FLICE-like inhibitory protein. The American journal of pathology, 169(5), 1833-1842.
- Kim, E. J., Park, S. Y., Shin, H. K., Kwon, D. Y., Surh, Y. J., & Park, J. H. Y. (2007). Activation of caspase-8 contributes to 3, 3′-Diindolylmethane-induced apoptosis in colon cancer cells. The Journal of nutrition, 137(1), 31-36.
- Li, Y., Wang, Z., Kong, D., Murthy, S., Dou, Q. P., Sheng, S., … & Sarkar, F. H. (2007). Regulation of FOXO3a/β-catenin/GSK-3β signaling by 3, 3′-diindolylmethane contributes to inhibition of cell proliferation and induction of apoptosis in prostate cancer cells. Journal of Biological Chemistry, 282(29), 21542-21550.
- Ichite, N., Chougule, M. B., Jackson, T., Fulzele, S. V., Safe, S., & Singh, M. (2009). Enhancement of docetaxel anticancer activity by a novel diindolylmethane compound in human non–small cell lung cancer. Clinical Cancer Research, 15(2), 543-552.
- Kandala, P. K., & Srivastava, S. K. (2010). Activation of checkpoint kinase 2 by 3, 3′-diindolylmethane is required for causing G2/M cell cycle arrest in human ovarian cancer cells. Molecular pharmacology, 78(2), 297-309.
- Kassie, F., Anderson, L. B., Scherber, R., Yu, N., Lahti, D., Upadhyaya, P., & Hecht, S. S. (2007). 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 Research, 67(13), 6502-6511.
- Kassie, F., Melkamu, T., Endalew, A., Upadhyaya, P., Luo, X., & Hecht, S. S. (2010). Inhibition of lung carcinogenesis and critical cancer-related signaling pathways by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine, indole-3-carbinol and myo-inositol, alone and in combination. Carcinogenesis, 31(9), 1634-1641.
- Carter, T. H., Liu, K., Ralph Jr, W., Chen, D., Qi, M., Fan, S., … & Auborn, K. J. (2002). Diindolylmethane alters gene expression in human keratinocytes in vitro. The Journal of nutrition, 132(11), 3314-3324.
- Leong, H., Firestone, G. L., & Bjeldanes, L. F. (2001). Cytostatic effects of 3, 3′-diindolylmethane in human endometrial cancer cells result from an estrogen receptor-mediated increase in transforming growth factor-αCarcinogenesis, 22(11), 1809-1817.
- Li, Y., Li, X., & Guo, B. (2010). Chemopreventive agent 3, 3′-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. Cancer research, 70(2), 646-654.
- Gamet-Payrastre, L., Lumeau, S., Gasc, N., Cassar, G., Rollin, P., & Tulliez, J. (1998). Selective cytostatic and cytotoxic effects of glucosinolates hydrolysis products on human colon cancer cells in vitro. Anti-cancer drugs, 9(2), 141-148.
- Kassie, F., Anderson, L. B., Scherber, R., Yu, N., Lahti, D., Upadhyaya, P., & Hecht, S. S. (2007). 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 Research, 67(13), 6502-6511
- Le, H. T., Schaldach, C. M., Firestone, G. L., & Bjeldanes, L. F. (2003). Plant-derived 3, 3′-diindolylmethane is a strong androgen antagonist in human prostate cancer cells. Journal of Biological Chemistry, 278(23), 21136-21145.
- Bhuiyan, M. M., Li, Y., Banerjee, S., Ahmed, F., Wang, Z., Ali, S., & Sarkar, F. H. (2006). 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 research, 66(20), 10064-10072.
- Vivar, O. I., Lin, C. L., Firestone, G. L., & Bjeldanes, L. F. (2009). 3, 3′-Diindolylmethane induces a G1 arrest in human prostate cancer cells irrespective of androgen receptor and p53 status. Biochemical pharmacology, 78(5), 469-476.
- Wu, T. Y., Huang, Y., Zhang, C., Su, Z. Y., Boyanapalli, S., Khor, T. O., … & Kong, A. N. T. (2015). Pharmacokinetics and pharmacodynamics of 3, 3′-diindolylmethane (DIM) in regulating gene expression of phase II drug metabolizing enzymes. Journal of pharmacokinetics and pharmacodynamics, 42(4), 401-408.
- Chang, X., Tou, J. C., Hong, C., Kim, H. A., Riby, J. E., Firestone, G. L., & Bjeldanes, L. F. (2005). 3, 3′-Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic mice. Carcinogenesis, 26(4), 771-778.
- Kong, D., Li, Y., Wang, Z., Banerjee, S., & Sarkar, F. H. (2007). Inhibition of angiogenesis and invasion by 3, 3′-diindolylmethane is mediated by the nuclear factor–κB downstream target genes MMP-9 and uPA that regulated bioavailability of vascular endothelial growth factor in prostate cancer. Cancer research, 67(7), 3310-3319.
- Ahmad, A., Kong, D., Sarkar, S. H., Wang, Z., Banerjee, S., & Sarkar, F. H. (2009). Inactivation of uPA and its receptor uPAR by 3, 3′‐diindolylmethane (DIM) leads to the inhibition of prostate cancer cell growth and migration. Journal of cellular biochemistry, 107(3), 516-527.
- Cho, H. J., Seon, M. R., Lee, Y. M., Kim, J., Kim, J. K., Kim, S. G., & Park, J. H. Y. (2008). 3, 3′-Diindolylmethane suppresses the inflammatory response to lipopolysaccharide in murine macrophages. The Journal of nutrition, 138(1), 17-23.
- Kim, E. J., Park, H., Kim, J., & Park, J. H. Y. (2010). 3, 3′‐diindolylmethane suppresses 12‐O‐tetradecanoylphorbol‐13‐acetate‐induced inflammation and tumor promotion in mouse skin via the downregulation of inflammatory mediators. Molecular carcinogenesis, 49(7), 672-683.
- Kim, Y. H., Kwon, H. S., Kim, D. H., Shin, E. K., Kang, Y. H., Yoon Park, J. H., … & Kim, J. K. (2009). 3, 3′-diindolylmethane attenuates colonic inflammation and tumorigenesis in mice. Inflammatory bowel diseases, 15(8), 1164-1173.
- Dong, L., Xia, S., Gao, F., Zhang, D., Chen, J., & Zhang, J. (2010). 3, 3′-Diindolylmethane attenuates experimental arthritis and osteoclastogenesis. Biochemical pharmacology, 79(5), 715-721.
- Parkin, D. R., & Malejka-Giganti, D. (2004). 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 Detection and Prevention, 28(1), 72-79.
- Rogan, E. G. (2006). The natural chemopreventive compound indole-3-carbinol: state of the science. in vivo, 20(2), 221-228.
- Jellinck, P. H., Makin, H. L., Sepkovic, D. W., & Bradlow, H. L. (1993). Influence of indole carbinols and growth hormone on the metabolism of 4-androstenedione by rat liver microsomes. The Journal of steroid biochemistry and molecular biology, 46(6), 791-798.
- Yang, G., Wang, Y., Tian, J., & Liu, J. P. (2013). Huperzine A for Alzheimer’s disease: a systematic review and meta-analysis of randomized clinical trials. PloS one, 8(9), e74916.
- Riby, J. E., Chang, G. H., Firestone, G. L., & Bjeldanes, L. F. (2000). Ligand-independent activation of estrogen receptor function by 3, 3′-diindolylmethane in human breast cancer cells. Biochemical pharmacology, 60(2), 167-177.
- Leong, H., Riby, J. E., Firestone, G. L., & Bjeldanes, L. F. (2004). 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. Molecular Endocrinology, 18(2), 291-302.
- Del Priore, G., Gudipudi, D. K., Montemarano, N., Restivo, A. M., Malanowska-Stega, J., & Arslan, A. A. (2010). Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecologic oncology, 116(3), 464-467.
- Heath, E. I., Heilbrun, L. K., Li, J., Vaishampayan, U., Harper, F., Pemberton, P., & Sarkar, F. H. (2010). A phase I dose-escalation study of oral BR-DIM (BioResponse 3, 3′-Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. American journal of translational research, 2(4), 402.
- Castanon, A., Tristram, A., Mesher, D., Powell, N., Beer, H., Ashman, S., … & Sasieni, P. (2012). Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. British journal of cancer, 106(1), 45-52.
- Yerushalmi, R., Bargil, S., Ber, Y., Ozlavo, R., Sivan, T., Rapson, Y., … & Margel, D. (2020). 3, 3-Diindolylmethane (DIM): a nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial. Carcinogenesis, 41(10), 1395-1401.
- Olenina, L., Patel, I. P., & Portal, A. P. Health Information Indole-3-Carbinol.
- Balk, J. L. (2000). Indole-3-carbinol for cancer prevention. Altern Med Alert, 3, 105-107.
- Olenina, L., Patel, I. P., & Portal, A. P. Health Information Indole-3-Carbinol.
- Lake, B. G., Tredger, J. M., Renwick, A. B., Barton, P. T., & Price, R. J. (1998). 3, 3′-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. Xenobiotica, 28(8), 803-811.
- Jellinck, P. H., Gekforkert, P., Riddick, D. S., Okey, A. B., Michnovicz, J. J., & Bradlow, H. L. (1993). Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation. Biochemical pharmacology, 45(5), 1129-1136.
- Heath, E. I., Heilbrun, L. K., Li, J., Vaishampayan, U., Harper, F., Pemberton, P., & Sarkar, F. H. (2010). A phase I dose-escalation study of oral BR-DIM (BioResponse 3, 3′-Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. American journal of translational research, 2(4), 402.
- Thomson, C. A., Chow, H. H., Wertheim, B. C., Roe, D. J., Stopeck, A., Maskarinec, G., … & Thompson, P. A. (2017). A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast cancer research and treatment, 165(1), 97-107.
- Rajoria, S., Suriano, R., Parmar, P. S., Wilson, Y. L., Megwalu, U., Moscatello, A., Bradlow, H. L., Sepkovic, D. W., Geliebter, J., Schantz, S. P., & Tiwari, R. K. (2011). 3,3′-diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study. Thyroid : official journal of the American Thyroid Association, 21(3), 299–304. https://doi.org/10.1089/thy.2010.0245
- Hsu, E. L., Chen, N., Westbrook, A., Wang, F., Zhang, R., Taylor, R. T., & Hankinson, O. (2008). CXCR4 and CXCL12 down-regulation: a novel mechanism for the chemoprotection of 3, 3′-diindolylmethane for breast and ovarian cancers. Cancer letters, 265(1), 113-123.
- Leong, H., Firestone, G. L., & Bjeldanes, L. F. (2001). Cytostatic effects of 3, 3′-diindolylmethane in human endometrial cancer cells result from an estrogen receptor-mediated increase in transforming growth factor-α expression. Carcinogenesis, 22(11), 1809-1817.