Radiosensitization by inhibition of cell survival signal

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Sulforaphane (SFN), an isothiocyanate present in broccoli, is one of the most promising chemopreventive agents. It inhibits cell proliferation and induces apoptosis in different tumor cell lines, suggesting that SFN might be useful as chemotherapeutic agent for cancer treatment. In this study, we investigated the radiosensitizing effect of SFN in two human pancreatic cancer cell lines, MIA PaCA-2 and PANC-1. Radiation survival curves obtained showed that SFN radiosensitized both cell lines, but potentiated X-ray sensitivity more in MIAPaCa-2 than PANC-1 cells. In addition, SFN radiosensitized MIA PaCA-2 cells to apoptosis, but not PANC-1. The results obtained indicates that SFN-mediated radiosensitization by inducing apoptosis in MIA PaCa-2 cells is not regulated by Bc1-2 and Bax. A combined treatment of SFN and X-rays resulted in a decrease in the level of XIAP in both cells. MIA PaCa-2 cells treated with SFN and X-rays exhibited a marked increase in protein level of Apaf-1, which is essential for activation of.caspase-9. These results indicate that Apaf-1 is an important role in SFN-induced radiosensization by inducing apoptosis. Thus, SFN appears to be a promising radiosensitizing agent for use against human carcinomas.