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 μ M concentrations of these compounds for 24 hr 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 hr 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 (Panc28) hr and correlated with previous studies on the role of survivin in radiation-resistance. However, in cells cotreated with γ -radiation plus DIM-C-pPhBr or 2,2 ′ -diMeDIM-C-pPhBr, induction of survivin by γ -radiation was inhibited after cotreatment with both compounds, suggesting applications for these drugs in combination cancer chemotherapy with γ radiation.