Apoptotic signaling induced by benzamide riboside: an in vitro study.

Benzamide riboside (BR) is a novel anticancer agent exhibiting potent cytotoxic activity in malignant cell lines. However, the mechanism of induction of apoptosis is not clear. The purpose of this study was to elucidate the apoptotic signaling induced by BR on different human cancer cell lines. Our results revealed that BR at a dose of 50 microM induces apoptosis in SiHa, Hep2, and Ca Ski cells as studied by morphology and flow cytometry. A downregulation of anti-apoptotic proteins Bcl-2 and Bcl-xL was observed, whereas the expression level of the pro-apoptotic protein Bax remained unaffected. An upregulation of p53 was observed while no change was seen on the level of apoptosis inducing factor (AIF). A significant increase in caspase-3 and -9 activities was seen, which was accompanied by PARP cleavage. Release of cytochrome c from the mitochondria to the cytosol was also observed. Taken together, the findings suggest that BR induces apoptosis in SiHa, Hep2, and Ca Ski cells via the intrinsic mitochondrial pathway.