For research use only. Not Intended for Therapeutic Use!
|IC50:||65 uM (SKOV-3 cell, 72h)|
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DIM (3,3/'-diindolylmethane), a small molecule compound, is a proposed cancer preventive agent.
in vitro: DIM caused rapid activation of ataxia-telangiectasia mutated (ATM), a nuclear kinase that regulates responses to DNA damage (DDR) and oxidative stress. Subsequently, multiple ATM substrates were phosphorylated, suggesting that DIM induces an ATM-dependent DDR-like response, and DIM enhanced radiation-induced ATM signaling and NF-κB activation. DIM also caused activation of ATM in rodent tissues. Activation of ATM by DIM may be due, in part, to inhibition of protein phosphatase 2A, an upstream regulator of ATM . DIM significantly inhibited the proliferation of human gastric cancer cells in a dose-dependent manner. The percentage of G1 phase cells increased 24 h following DIM treatment. DIM reduced CDK2, CDK4, CDK6 and cyclin D1 protein levels, while increasing p53 protein levels. DIM induced the levels of cleaved poly(ADP-ribose) polymerase, cleaved-caspase-9, and diminished pro-caspase-3 protein production. In addition, DIM increased pLATS1, Mob1, pMob1, pYAP and Ras association domain family 1 (RASSF1) protein levels and reduced Yap protein production levels .
in vivo: Among treatment groups, the mice administered with I3C and DIM, DIM shows decreased glucose, insulin and HbA1c and increased Hb and glycogen content in liver when compared to I3C, which was comparable with the standard drug metformin . DIM significantly suppressed the growth of ovarian tumors in vivo. Tumor growth suppressive effects of DIM in SKOV-3 tumor xenografts were associated with reduced phosphorylation of EGFR, MEK, and ERK . Toxicity: No induction of CYP1B1 in the colon was observed in either sex. Long-term exposure to DIM produced no observable toxicity, and comparison to I3C indicates that DIM is a markedly less efficacious inducer of CYP in the rat at doses relevant to human supplementation .
. Prabodh K, et al. Activation of Checkpoint Kinase 2 by 3,3-Diindolylmethane Is Required for Causing G2/M Cell Cycle Arrest in Human Ovarian Cancer Cells. Mol Pharmacol 78:297-309, 2010
. Fan S, et al. DIM (3,3/'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism. Proc Natl Acad Sci U S A. 2013 Oct 14.
. Poornima J, et al. Regulation of carbohydrate metabolism by indole-3-carbinol and its metabolite 3,3/'-diindolylmethane in high-fat diet-induced C57BL/6J mice. Mol Cell Biochem. 2013 Sep 27.
. Li XJ, et al. 3,3/'-Diindolylmethane suppresses the growth of gastric cancer cells via activation of the Hippo signaling pathway. Oncol Rep. 2013 Nov;30(5):2419-26.
. Kandala PK, et al. Blocking epidermal growth factor receptor activation by 3,3/'-diindolylmethane suppresses ovarian tumor growth in vitro and in vivo. J Pharmacol Exp Ther. 2012 Apr;341(1):24-32.
. Leibelt DA, et al. Evaluation of chronic dietary exposure to indole-3-carbinol and absorption-enhanced 3,3/'-diindolylmethane in sprague-dawley rats. Toxicol Sci. 2003 Jul;74(1):10-21.