TY - JOUR
T1 - 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
AU - Sreevalsan, Sandeep
AU - Jutooru, Indira
AU - Chadalapaka, Gayathri
AU - Walker, Michael
AU - Safe, Stephen
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - DIM analogs
KW - Survivin downregulation
KW - γ-radiation-induced survivin
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U2 - 10.3892/ijo-00000436
DO - 10.3892/ijo-00000436
M3 - Article
C2 - 19787275
AN - SCOPUS:70449579240
SN - 1019-6439
VL - 35
SP - 1191
EP - 1199
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 5
ER -