1,1-Bis(3′-indolyl)-1-(p-bromophenyl)methane and related compounds repress survivin and decrease γ-radiation-induced survivin in colon and pancreatic cancer cells

1,1-Bis(3′-indolyl)-1-(p-bromophenyl)methane (DIM-C-pPhBr) and the 2,2′-dimethyl analog (2,2′-diMeDIM-C-pPhBr) inhibit proliferation and induce apoptosis in SW480 colon and Panc28 pancreatic cancer cells. In this study, treatment with 10-20 μM concentrations of these compounds for 24 h induced cleaved PARP and decreased survivin protein and mRNA expression in both cell lines. However, results of time course studies show that DIM-C-pPhBr and 2,2′-diMeDIM-C-pPhBr decrease survivin protein within 2 h after treatment, whereas survivin mRNA levels were decreased only at later time-points indicating activation of transcription-independent and -dependent pathways for downregulation of survivin. In addition, we also observed that γ-radiation inhibited pancreatic and colon cancer cell growth and this was associated with enhanced expression of survivin after 24 (SW480) or 24 and 48 h (Panc28) and correlated with previous studies on the role of survivin in radiation- resistance. However, in cells co-treated with γ-radiation plus DIM-C-pPhBr or 2,2′-diMeDIM-C-pPhBr, induction of survivin by γ-radiation was inhibited after co-treatment with both compounds, suggesting applications for these drugs in combination cancer chemotherapy with γ-radiation.