Abstract
Isothiocyanates (ITC; chemical structure: R-N=C=S) are present in cruciferous vegetables such as broccoli, cabbage and cauliflowers. Some ITSs have been shown to be effective in preventing chemically induced cancer. Benzyl isothiocyanate (BITC), an ITC compound isolated from papaya, has been reported to prevent cancers through the induction of Phase II detoxification enzymes in animal models, and induce apoptosis in human maligmant cell lines. These findings suggest that BITC could be a useful chemopreventive and/or chemotherapeutic agent against human cancers. We investigated the effect of BITC on the radiosentitivity in two human panreatic cancer cell lines, MIA PaCa-2 and Panc-1 carrying mutant p53. BITC sentitized both cell lines to radiation, but potentiated X-ray sentitivity more in MIA PaCa-2 cells. A combination of BITC and radiation induced apoptosis synergistically and cleavage of PARP in MIA PaCA-2, but not Panc-1 cells. Next, we determined the effect of BITC treatment on the level of Apaf-1 protein, which plays an important role in regulation of apoptosis. The BITC-treated MIA PaCa-2 cells exhibited a marked increase in protein level of Apaf-1. These results indicate that BITC induces radiosentitization through the suppression of anti-apoptosis signal and increase of apoptosis promotion factor in human certain cancer cells. Thus, Isothiocyanate, iucluding BITC, may present a new class of radiosensitization in clinical radiation therapy.
