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Prostate Cancer Chemoprevention: I3C and DIM

Increasing serum levels of phytochemical DIM may be chemopreventive and chemoprotective for prostate cancer.

Cruciferous Cabbage Family vegetables such as (including cabbage, cauliflower, Brussels sprouts, broccoli, kale, arugula, bok choy and more ) are rich in dietary phytochemicals including Sulforaphane-Glucosinolate family molecules 13C (Indole-3-Carbinol) and it’s major bioactive therapeutic metabolite DIM  (3 3’di-indole methane).

Chopping, chewing, massaging and lightly steaming cruciferous vegetables activates the plants own catalyzing myrosinase enzyme and exposing the plant to the acid environment in the stomach leading to further metabolism resulting in bio available and bio active DIM.  DIM levels can be measured in the serum.

There are numerous studies on the benefits of dietary consumption of cruciferous vegetables.. A high intake of cruciferous vegetables is associated with reduced risk of several human cancers.  There are strong associations between high intake of broccoli and breast cancer and prostate cancer in humans.  Human cell studies show inhibition of  cell growth of several cancers including breast, prostate, pancreatic, colorectal, lung and head and neck cancers.

DIM and Prostate Cancer

DIM

DIM appears to be a potent inhibitor of human androgen hormones which may promote expression of androgen receptors on prostate cancer cells which may lead to carcinogenesis. Increasing serum levels of DIM through diet and supplementation may therefore be chemopreventive for prostate cancer.

Human and Cell Studies have shown that increased serum levels of DIM 

  • Reduces Serum Prostate Specific Antigen
  • Reduces Serum Androgen Hormones
  • Down Regulates Prostate Stem Cell Activity
  • Decreases  Nuclear Androgen Receptors
  • Induces p450 metabolic detoxification enzymes CYP1A1, CYP1A2 and CYP1B
  • Decreases oxidative stress via nrf2-KEAP pathway

The OutSmart Cancer® System is focused upon transforming the tumor microenvironment  which is a signaling environment, so that there is less physiologic support for the development and spread of cancer.   In a health model (rather than a disease model) we endeavor to transform the biosystem and  reduce pro-carcinogenic and proliferative signaling and prevent cellular, nuclear and mitochondrial damage.

brocolli

Therefore we use phytochemicals such as I3C and DIM and dietary interventions to influence carcinogenic and proliferative signaling in the tumor microenvironment.

Guidelines for Increasing Serum DIM levels

Primary Reference

*Amare DE. Anti-Cancer and Other Biological Effects of a Dietary Compound 3,3ʹ-Diindolylmethane Supplementation: A Systematic Review of Human Clinical Trials. Nutrition and Dietary Supplements. 2020;12:123-137

https://doi.org/10.2147/NDS.S261577

Additional Selected References 

  1. Anderton MJ, Manson MM, Verschoyle RD, 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(15):5233–5241. doi:10.1158/1078-0432.CCR-04-0163
  2. Bjeldanes LF, Kim JY, Grose KR, et al. 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 S A. 1991;88(21):9543–9547. doi:10.1073/pnas.88.21.9543
  3. Chang Y-C, Riby J, Chang GH-F, et al. 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(5):825–834. doi:10.1016/S0006-2952(99)00165-3
  4. Chen I, McDougal A, Wang F, et al. Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Carcinogenesis. 1998;19(9):1631–1639. doi:10.1093/carcin/19.9.1631
  5. Bradfield CA, Bjeldanes LF. High-performance liquid chromatographic analysis of anticarcinogenic indoles in Brassica oleracea. J Agric Food Chem. 1987;35(1):46–49. doi:10.1021/jf00073a010
  6. Weng J-R, Tsai C-H, Kulp SK, et al. Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer Lett. 2008;262(2):153–163. doi:10.1016/j.canlet.2008.01.033
  7. Bradlow HL. Indole-3-carbinol as a chemoprotective agent in breast and prostate cancer. In Vivo. 2008;22(4):441–445
  8. Ahmad A, Ali S, Wang Z, et al. 3, 3′‐diindolylmethane enhances taxotere‐induced growth inhibition of breast cancer cells through downregulation of FoxM1. Int J Cancer. 2011;129(7):1781–1791. doi:10.1002/ijc.25839
  9. Ali S, Banerjee S, Ahmad A, et al. Apoptosis-inducing effect of erlotinib is potentiated by 3,3ʹ-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer. Mol Cancer Ther. 2008;7(6):1708–1719. doi:10.1158/1535-7163.MCT-08-0354
  10. Banerjee S, Wang Z, Kong D, et al. 3, 3′-Diindolylmethane enhances chemosensitivity of multiple chemotherapeutic agents in pancreatic cancer. Cancer Res. 2009;69(13):5592–5600. doi:10.1158/0008-5472.CAN-09-0838
  11. Giovannucci E, Rimm EB, Liu Y, et al. A prospective study of cruciferous vegetables and prostate cancer. Cancer Epidemiol Prev Biomarkers. 2003;12(12):1403–1409.
  12. Kong D, Heath E, Chen W, et al. Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM. PLoS One. 2012;7(3):e33729. doi:10.1371/journal.pone.0033729
  13. Abdelbaqi K,Lack N, Guns ET, et al. Antiandrogenic and growth inhibitory effects of ring‐substituted analogs of 3, 3′‐diindolylmethane (Ring‐DIMs) in hormone‐responsive LNCaP human prostate cancer cells. Prostate. 2011;71(13):1401–1412.
  14. Bhattacharjee S, Dashwood RH. Epigenetic Regulation of NRF2/KEAP1 by Phytochemicals. Antioxidants. 2020; 9(9):865. https://doi.org/10.3390/antiox9090865
  15. Li Y et al. Recent progress on nutraceutical research in prostate cancer. Cancer Metastasis Rev. 2014;33(2-3):629-640.