Benzyl isothiocyanate sensitizes human pancreatic cancer cells to radiation therapy

Abstract

Increase in systemic toxicity and resistance are the major drawbacks of radiation therapy in the treatment of pancreatic cancer. We have shown previously that BITC inhibits the growth of human pancreatic cancer cells and induces apoptosis. Here we determined whether BITC could sensitize BxPC-3 cells and increase the therapeutic potential of γ-irradiation. Cells were pretreated with 2.5μM BITC for 24h followed by exposure to 5Gy of γ-irradiation and were allowed to grow for another 24 or 48h before being analyzed. Combination of BITC and γ-irradiation significantly reduced survival of cells and caused significantly enhanced arrest of cells in G2/M phase as compared to cells exposed to γ-irradiation alone. G2/M arrest was associated with DNA damage leading to the phosphorylation of ATR (Ser-428), Chk2 (Thr-68), Cdc25C (Ser-216), Cdk-1 (Tyr-15) and induction of p21 Waf1/Cip1. However, combination treatment after 48h caused 2.8-fold increase in apoptosis in BxPC-3 cells. Apoptosis at 48h was associated with NF-kB inhibition and p38 activation. Taken together, results of the present study suggest that the apoptosis-inducing effect of γ-irradiation can be increased by BITC.