Article

Indole-3-carbinol as a Chemoprotective Agent in Breast and Prostate Cancer

David and Alice Jurist Institute for Medical Research, Hackensack University Medical Center Hackensack, NJ 07601, USA.
In vivo (Athens, Greece) (Impact Factor: 1.15). 07/2008; 22(4):441-5.
Source: PubMed

ABSTRACT Assessment of the oral use of indole-3-carbinol (I3C) as a chemoprotective compound has not sufficiently considered the chemical instability of I3C. This review addresses the question of whether I3C is directly active in its own right or only serves as a precursor, with all of the biological responses coming from reaction products arising in culture media and in the presence of stomach acid. Because of the rapid conversion of I3C into its dimer. diindolylmethane (DIM), and trimers very little circulating I3C is present following oral use to effect a biological response. Reports of toxicity associated with oral use of I3C relate to unfavorable enzyme induction, which can be attributed to non-DIM reaction products. Because DIM provides a predictable, safer response than the mélange of compounds derived from I3C DIM should be regarded as the chemoprotective compound of choice.

Download full-text

Full-text

Available from: Leon H Leon Bradlow, Jul 02, 2015
0 Followers
 · 
38 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cervical screening identifies many women with low-grade abnormalities. In vitro and in vivo studies have shown that diindolylmethane (DIM) could potentially halt (cervical) carcinogenesis. We report on a randomised controlled trial of the effect of DIM in women with low-grade cervical cytological abnormalities. We conducted a pragmatic double-blind, randomised controlled trial of 150 mg DIM (from BioResponse DIM) or placebo daily for 6 months in women with newly diagnosed, low-grade cytological abnormalities. Randomisation was in the ratio 2 (DIM) to 1 (placebo). All women were invited for colposcopy at 6 months with biopsy of any abnormality. Of the 551 randomised women available for analysis, 9% on DIM and 12% on placebo had cervical intraepithelial neoplasia-2 (CIN2) or worse after 6-month supplementation (risk ratio (RR) 0.7 (95% confidence interval (CI): 0.4-1.2)), whereas 4.6% and 5.1%, respectively, had CIN3 or worse (RR 0.9 (95% CI: 0.4-2.0)). A total of 27.3% of women on DIM and 34.3% on placebo had no sign of disease (negative cytology, colposcopy and human papilloma virus (HPV) tests) at 6 months (RR 0.8 (95% CI: 0.6-1.0)). Of those HPV-positive at baseline, 69% (114 out of 166) of the DIM group were positive at 6 months compared with 61% (43 out of 71) of the placebo group: RR 1.1 (95% CI: 0.9-1.4). Diindolylmethane supplementation was well tolerated. The results suggest that short-term DIM supplementation (150 mg day(-1)) is well tolerated, but is unlikely to have an effect on cytology or HPV infection. Uncertainty remains regarding its effect on CIN2+.
    British Journal of Cancer 11/2011; 106(1):45-52. DOI:10.1038/bjc.2011.496 · 4.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study employed cultured human primary hepatocytes to investigate the ability of the putative chemopreventive phytochemicals curcumin (CUR), 3,3'-diindolylmethane (DIM), isoxanthohumol (IXN), or 8-prenylnaringenin (8PN) to reduce DNA adduct formation of the hepatocarcinogen aflatoxin B1 (AFB). Following 48 h of pretreatment, DIM and 8PN significantly increased AFB-DNA adduct levels, whereas CUR and IXN had no effect. DIM greatly enhanced the transcriptional expression of cytochrome P450 (CYP) 1A1 and CYP1A2 mRNA. Glutathione S-transferase mRNAs were not increased by any of the treatments. In vitro enzyme activity assays demonstrated that 8PN and DIM, but not CUR or IXN, inhibited human CYP1A1, CYP1A2, and CYP3A4 activities. To distinguish between treatment effects on transcription versus direct effects on enzyme activity for DIM, we evaluated the effects of pretreatment alone (transcriptional activation) versus cotreatment alone (enzyme inhibition). The results demonstrated that effects on gene expression, but not catalytic activity, are responsible for the observed effects of DIM on AFB-DNA adduct formation. The increase in AFB-DNA damage following DIM treatment may be explained through its substantial induction of CYP1A2 and/or its downregulation of GSTM1, both of which were significant. The increase in DNA damage by DIM raises potential safety risks for dietary supplements of DIM and its precursor indole-3-carbinol.
    Toxicological Sciences 09/2009; 112(2):303-10. DOI:10.1093/toxsci/kfp206 · 4.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although estradiol itself is primarily responsible for female development, the metabolites are responsible for many of the other positive and negative properties of estrogens. Phase I metabolism of estradiol is exclusively oxidative unlike the other steroid hormones and involves a series of hydroxylations. The specific hydroxylations can be induced or suppressed by endogenous or exogenous compounds that influence the cytochrome enzymes that act on specific sites on the molecule. Modulation of estrogen hydroxylation is essential since some of the other metabolites increase the risk of breast and other hormone-related cancers. The various hydroxylation pathways are discussed as well as the effects of the products of estrogen hydroxylation. The interaction between the human papilloma virus (HPV) and 16alpha-hydroxyestrone is discussed with reference to recurrent respiratory papillomatosis, cervical dysplasia, and cervical cancer. The role of estrogen metabolites in predicting the relative risk for breast cancer is evaluated using prospective and case-control studies. In one pilot study a factor that is a component of body fat is identified to be an inhibitor of estrogen C-2 hydroxylation. The role of environmental toxins like the phthalate esters and how these compounds increase risk for hormonal cancers is examined in a second pilot study.
    Annals of the New York Academy of Sciences 03/2009; 1155(1):57-67. DOI:10.1111/j.1749-6632.2008.03675.x · 4.31 Impact Factor