Uttam Pal - 2,2'-diphenyl-3,3'-diindolylmethane: a potent compound induces apoptosis in breast cancer cells by inhibiting EGFR pathway

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      Bhowmik, Arijit, Das, Nilanjana, Pal, Uttam, Mandal, Madhumita,   Bhattacharya, Seemana, Sarkar, Moumita, Jaisankar, Parasuraman,   Maiti, Nakul C, Ghosh, Mrinal K 8 (3) e59798-

      Abstract: Despite recent advances in medicine,   30-40% of patients with breast cancer show recurrence   underscoring the need for improved effective therapy. In this   study, by in vitro screening we have selected a novel synthetic   indole derivative 2,2'-diphenyl-3,3'-diindolylmethane (DPDIM) as   a potential anti- breast cancer agent. DPDIM induces apoptosis   both in vitro in breast cancer cells MCF7, MDA-MB 231 and MDA-MB   468 and in vivo in 7,12-dimethylbenz[α]anthracene (DMBA) induced   Sprague-Dawley (SD) rat mammary tumor. Our in vitro studies show   that DPDIM exerts apoptotic effect by negatively regulating the   activity of EGFR and its downstream molecules like STAT3, AKT and   ERK1/2 which are involved in the proliferation and survival of   these cancer cells. In silico predictions also suggest that DPDIM   may bind to EGFR at its ATP binding site. DPDIM furthermore   inhibits EGF induced increased cell viability. We have also shown   decreased expression of pro-survival factor Bcl-XL as well as   increase in the level of pro-apoptotic proteins like Bax, Bad,   Bim in DPDIM treated cells in vitro and in vivo. Our results   further indicate that the DPDIM induced apoptosis is mediated   through mitochondrial apoptotic pathway involving the   caspase-cascade. To the best of our knowledge this is the first   report of DPDIM for its anticancer activity. Altogether this   report suggests that DPDIM could be an effective therapeutic   agent for breast cancer.

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