Indole-3-carbinol as a Chemoprotective Agent in Breast and Prostate Cancer
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.
Full-textDOI: · Available from: Leon H Leon Bradlow, Sep 26, 2015
- SourceAvailable from: Kang Mo Ku
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- "Despite significant increases in glucobrassicin, I3C and DIM hydrolysis product concentrations in kale extracts were relatively low. I3C has been reported to be highly instable  and will react with other substrates generating by-products by condensation with ascorbic acid or through oligomerization . Following hydrolysis of the parent GS, relatively higher levels of NI3C were observed than I3C. "
ABSTRACT: Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties 'Dwarf Blue Curled Vates' and 'Red Winter' in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar 'Red Winter' in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined increases in phenolics (quercetin and kaempferol) and GS hydrolysis product concentrations rather than by individual products alone.PLoS ONE 07/2014; 9(8):e103407. DOI:10.1371/journal.pone.0103407 · 3.23 Impact Factor
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- "Prostate cancer risk has been shown to be inversely correlated with the consumption of cruciferous vegetables , . In particular, sulforaphane (SFN) and 3,3′-diindolylmethane (DIM), two phytochemicals derived from glucosinolates in cruciferous vegetables have been demonstrated to be effective chemopreventive agents against prostate cancer , . SFN is an isothiocyanate derived from the hydrolysis of glucoraphanin, and DIM is a major acid condensation product of indole-3-carbinol (I3C), a hydrolysis product of glucobrassicin. "
ABSTRACT: Epigenetic changes, including aberrant DNA methylation, result in altered gene expression and play an important role in carcinogenesis. Phytochemicals such as sulforaphane (SFN) and 3,3'-diindolylmethane (DIM) are promising chemopreventive agents for the treatment of prostate cancer. Both have been shown to induce re-expression of genes, including tumor suppressor genes silenced in cancer cells, via modulation of epigenetic marks including DNA methylation. However, it remained unclear the effects SFN and DIM on DNA methylation at a genomic scale. The goal of this study was to determine the genome-wide effects of SFN and DIM on promoter methylation in normal prostate epithelial cells and prostate cancer cells. Both SFN and DIM treatment decreased DNA methyltransferase expression in normal prostate epithelial cells (PrEC), and androgen-dependent (LnCAP) and androgen-independent (PC3) prostate cancer cells. The effects of SFN and DIM on promoter methylation profiles in normal PrEC, LnCAP and PC3 prostate cancer cells were determined using methyl-DNA immunoprecipitation followed by genome-wide DNA methylation array. We showed widespread changes in promoter methylation patterns, including both increased and decreased methylation, in all three prostate cell lines in response to SFN or DIM treatments. In particular, SFN and DIM altered promoter methylation in distinct sets of genes in PrEC, LnCAP, and PC3 cells, but shared similar gene targets within a single cell line. We further showed that SFN and DIM reversed many of the cancer-associated methylation alterations, including aberrantly methylated genes that are dysregulated or are highly involved in cancer progression. Overall, our data suggested that both SFN and DIM are epigenetic modulators that have broad and complex effects on DNA methylation profiles in both normal and cancerous prostate epithelial cells. Results from our study may provide new insights into the epigenetic mechanisms by which SFN and DIM exert their cancer chemopreventive effects.PLoS ONE 01/2014; 9(1):e86787. DOI:10.1371/journal.pone.0086787 · 3.23 Impact Factor
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- "Both women and the health service would benefit from the existence of an effective natural medical treatment (using an oral preparation) for low-grade cytological lesions that would increase regression and reduce the need for excision. Indole-3-carbinol (I3C) and its dimer diindolylmethane (DIM) are found in cruciferous vegetables (Ciska et al, 2009) and have been identified as compounds that could potentially prevent or halt carcinogenesis (Bradlow, 2008; Ahmad et al, 2010). Diindolylmethane is naturally formed from I3C during acid digestion of cruciferous vegetables and I3C supplements (Reed et al, 2006; Ciska et al, 2009). "
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 · 4.84 Impact Factor