Benzyl isothiocyanate sensitizes human pancreatic cancer cells to radiation therapy.
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 gamma-irradiation. Cells were pretreated with 2.5 microM BITC for 24h followed by exposure to 5 Gy of gamma-irradiation and were allowed to grow for another 24 or 48 h before being analyzed. Combination of BITC and gamma-irradiation significantly reduced survival of cells and caused significantly enhanced arrest of cells in G2/M phase as compared to cells exposed to gamma-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 p21Waf1/Cip1. However, combination treatment after 48 h caused 2.8-fold increase in apoptosis in BxPC-3 cells. Apoptosis at 48 h was associated with NF-kappa B inhibition and p38 activation. Taken together, results of the present study suggest that the apoptosis-inducing effect of gamma-irradiation can be increased by BITC.
Sahu
Ravi Prakash
RP
Department of Pharmaceutical Sciences and Cancer Biology Center, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA.
Epperly
Michael Wayne
MW
Srivastava
Sanjay Kumar
SK
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects; D016195:G2 Phase / Q000187:drug effects* / Q000528:radiation effects; D005720:Gamma Rays / Q000627:therapeutic use*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000187:drug effects*
D017879:Isothiocyanates; D016328:NF-kappa B; C031403:benzyl isothiocyanate