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

Abstract

Abstract. 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 transcriptionindependent and -dependent pathways for downregulation of survivin. In addition, we also observed that Á-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 Á-radiation plus DIM-C-pPhBr or 2,2'-diMeDIM-C-pPhBr, induction of survivin by Á-radiation was inhibited after co-treatment with both compounds, suggesting applications for these drugs in combination cancer chemotherapy with Á-radiation.

Molecular Targets for Radiation Oncology in Prostate Cancer

“…Survivin is a member of the IAP gene family whose expression is associated with conservation of cell division and direct inhibition of caspases (Altieri, 2006 ). Upregulation of survivin expression has been shown in glioblastoma, colon, and pancreatic cells (Chakravarti et al, 2004 ; Sreevalsan et al, 2009 ). Intratumoral injection of an antisense against survivin or of an adenovirus expressing a dominant negative form of survivin, T34A, inhibits tumor growth and enhances sensitivity to anti-androgen therapy (O'Connor et al, 2000 ; Zhang et al, 2005 ).…”