Disease relevance of CCRIS 5806

• These results suggest that targeting survivin by 3,3'-diindolylmethane could be a new and novel approach for the prevention and/or treatment of breast cancer [1].
• Previous studies from our laboratory and others have shown the antiproliferative and proapoptotic effects of 3,3'-diindolylmethane (DIM) in prostate cancer cells [2].
• Fas-Mediated Apoptosis in Cholangiocarcinoma Cells Is Enhanced by 3,3'-Diindolylmethane through Inhibition of AKT Signaling and FLICE-Like Inhibitory Protein [3].
• We investigated the mechanism of ligand-independent activation of the estrogen receptor (ER) by 3,3'-diindolylmethane (DIM), a promising anticancer agent derived from vegetables of the Brassica genus, in Ishikawa and HEC-1B human endometrial cancer cells [4].
• 3,3'-diindolylmethane is a novel topoisomerase IIalpha catalytic inhibitor that induces S-phase retardation and mitotic delay in human hepatoma HepG2 cells [5].

High impact information on CCRIS 5806

• In contrast, the chemopreventative AHR ligand 3,3'-diindolylmethane promotes AHR nuclear translocation and p160 coactivator recruitment but, remarkably, fails to recruit Pol II or cause histone acetylation [6].
• Thus, we have established the critical role of enhanced mitochondrial ROS release in 3,3'-diindolylmethane-induced p21 up-regulation in human breast cancer cells [7].
• Gene expression profiling revealed survivin as a target of 3,3'-diindolylmethane-induced cell growth inhibition and apoptosis in breast cancer cells [1].
• To further elucidate the molecular mechanism(s) by which 3,3'-diindolylmethane exerts its effects on breast cancer cells, we have used microarray gene expression profiling analysis [1].
• We, therefore, hypothesized that down-regulation of survivin as observed by 3,3'-diindolylmethane could be an important approach for the treatment of breast cancer [1].

Chemical compound and disease context of CCRIS 5806

• Indole-3-carbinol, but not its major digestive product 3,3'-diindolylmethane, induces reversible hepatocyte hypertrophy and cytochromes P450 [8].

Biological context of CCRIS 5806

• Inhibition of nuclear translocation of nuclear factor-{kappa}B contributes to 3,3'-diindolylmethane-induced apoptosis in breast cancer cells [9].
• The phytochemical indole-3-carbinol (I3C), found in cruciferous vegetables, and its major acid-catalyzed reaction product 3,3'-diindolylmethane (DIM) showed anticancer activity mediated by its pleiotropic effects on cell cycle progression, apoptosis, carcinogen bioactivation, and DNA repair [1].
• We have tested our hypothesis using multiple molecular approaches and found that 3,3'-diindolylmethane inhibited cell growth and induced apoptosis in MDA-MB-231 breast cancer cells by down-regulating survivin, Bcl-2, and cdc25A expression and also caused up-regulation of p21(WAF1) expression, which could be responsible for cell cycle arrest [1].
• 3,3'-Diindolylmethane is a novel mitochondrial H(+)-ATP synthase inhibitor that can induce p21(Cip1/Waf1) expression by induction of oxidative stress in human breast cancer cells [7].
• Down-regulation of survivin by small interfering RNA before 3,3'-diindolylmethane treatment resulted in enhanced cell growth inhibition and apoptosis, whereas overexpression of survivin by cDNA transfection abrogated 3,3'-diindolylmethane-induced cell growth inhibition and apoptosis [1].

Anatomical context of CCRIS 5806

• Inhibition of growth factor-induced Ras signaling in vascular endothelial cells and angiogenesis by 3,3'-diindolylmethane [10].
• 3,3'-diindolylmethane (DIM) and its derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5 [11].
• We have previously shown that 3,3'-diindolylmethane (DIM) has a suppressive effect on the growth of human breast and PC cell lines [12].
• The effect of route of administration on the ability of indole-3-carbinol (13C), an anticarcinogen present in cruciferous vegetables, to induce estradiol 2-hydroxylase (EH) in female rat liver microsomes was investigated and compared to that of its main gastric conversion product, 3,3'-diindolylmethane (DIM) [13].
• 3,3'-Diindolylmethane, a cruciferous vegetable derived synthetic anti-proliferative compound in thyroid disease [14].

Associations of CCRIS 5806 with other chemical compounds

• Indole-3-carbinol, 3,3'-diindolylmethane, and indole-3-acetonitrile, three indoles occurring in edible cruciferous vegetables, have been studied for their effects on 7,12-dimethylbenz(a)anthracene-induced mammary tumor formation in female Sprague-Dawley rats and on benzo(a)pyrene-induced neoplasia of the forestomach in female ICR/Ha mice [15].
• The isothiocyanates sulforaphane and PEITC (beta-phenethyl isothiocyanate) as well as the indoles indole-3-carbinol and its condensation product 3,3'-diindolylmethane are known to inhibit cancer cell proliferation and induce apoptosis [16].
• Hepatic gene expression profiles were examined in trout after dietary exposure to 500 and 1500 ppm I3C and 3,3'-diindolylmethane (DIM), a major in vivo component of I3C, and were compared to the transcriptional signatures of two model hepatic tumor promoters: 17beta-estradiol (E2), an ER agonist, and beta-naphthoflavone, an AhR agonist [17].
• The in vitro and in vivo studies have demonstrated that some dietary components such as isoflavones, indole-3-carbinol (I3C), 3,3'-diindolylmethane (DIM), curcumin, (-)-epigallocatechin-3-gallate (EGCG), apigenin, etc., have shown inhibitory effects on human and animal cancers, suggesting that they may serve as chemopreventive agents [18].
• Immature Sprague-Dawley rats received daily doses of indole-3-carbinol (I3C, 0-1.5 g/kg/day), 3,3'-diindolymethane (DIM, 0-400 mg/kg/day), tamoxifen (TAM, 0-0.5 mg/kg/day), or vehicle to determine if their antiestrogenic effects occur by the same mechanism and whether I3C's action is mediated by DIM [19].

Gene context of CCRIS 5806

• 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 [4].
• 3,3'-Diindolylmethane (DIM) induces a G(1) cell cycle arrest in human breast cancer cells that is accompanied by Sp1-mediated activation of p21(WAF1/CIP1) expression [20].
• This study also shows that the AhR agonists benzo[a]pyrene, 3,3',4,4'-tetrachlorobiphenyl, chrysin, 6-methyl-1,3,8-trichlorodibenzofuran, and 3,3'-diindolylmethane also induce ERalpha-dependent transactivation [21].
• 3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices [22].
• 3,3'-Diindolylmethane and Paclitaxel Act Synergistically to Promote Apoptosis in HER2/Neu Human Breast Cancer Cells [23].

Analytical, diagnostic and therapeutic context of CCRIS 5806

• 3,3'-Diindolylmethane (DIM), a natural autolytic product in plants of the Brassica genus, including broccoli, cauliflower, and Brussels sprouts, exhibits promising cancer protective activities, especially against mammary neoplasia in animal models [24].
• Exposure of MCF-7 cells to 100 microM 3,3'-diindolylmethane for 24 h, 19% of apoptotic cells were detected by flow cytometry analysis [25].
• Physiological modeling of formulated and crystalline 3,3'-diindolylmethane pharmacokinetics following oral administration in mice [26].
• Exposure of the cells to 50 microM solution of 3,3'-diindolylmethane for 48 h, apoptosis (programmed cell death) was evidenced by the characteristic morphology of cell nuclei under fluorescence microscope and the DNA "ladder" in agarose gel electrophoresis [25].
• Western blot showed that wild-type p53 protein was unchanged after MCF-7 cells had been exposed to 50 microM 3,3'-diindolylmethane for 8 h [25].

References