Benzyl Isothiocyanate Induces Apoptosis in Human Pancreatic Cancer Cells by Inhibiting the Activation of Nuclear Factor-[kappa]B. Sanjay K. Srivastava and Shivendra V. Singh, Department of Pharmacology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213. Pancreatic cancer is a leading cause of cancer related deaths in the Western world with an overall one-year survival following diagnosis. Recent studies have revealed that nuclear factor-[kappa]B RelA (NF-[kappa]B), a transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Several lines of evidence suggest that NF-[kappa]B plays an important role in tumorigenesis and promotes cell survival by inhibiting apoptosis. In our previous study, we found that benzyl isothiocyanate (BITC), a naturally occurring chemopreventive agent present in cruciferous vegetables such as broccoli and cabbage was a potent inhibitor of the growth of cultured human pancreatic cancer cells Capan-2 and BxPC-3. Our results also demonstrated that BITC treatment arrested both the cells in G2/M phase and induced apoptosis. In the present study we provide experimental evidence to indicate that BITC-induced apoptosis is associated with inhibition of the activation of NF-[kappa]B pathway in BxPC-3 cells. Western blot analyses revealed time- and concentration-dependent inhibition of NF-[kappa]B/Rel-p65 protein expression in BxPC-3 cells upon exposure to growth suppressive concentrations of BITC. Increased expression of inhibitory subunit [kappa]B-[alpha] (I[kappa]B-[alpha]) in association with reduced phosphorylation at serine 32 was also observed in BITC treated cells. Consistent with these findings, BITC treatment resulted in reduced nuclear translocation of NF-[kappa]B as reflected by reduced DNA-binding capacity of NF-[kappa]B. Furthermore, activation of caspase-3 and cleavage of PARP was observed in BITC treated BxPC-3 cells. Interestingly, pharmacological inhibition of extracellular signal-regulated kinase (ERKs) further enhanced BITC-mediated suppression of NF-[kappa]B activation as well as antiproliferative activity of BITC. These results suggest that the inhibitory effects of BITC on the activation of NF-[kappa]B may be linked to MAPK pathway. This is the first report to implicate suppression of NF-[kappa]B activation as a potential mechanism for antiproliferative activity of BITC against human pancreatic cancer cells. Taken together, these findings suggest that BITC could be a potential chemopreventive agent against pancreatic cancer. (Supported by USPHS grant CA55589). AACR Abstract Number: LB-116, 2003 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.