Involvement of caspases in 5-FU induced apoptosis in an oral cancer cell line.

Although many anticancer drugs have been reported to induce apoptosis in cancer cells, the underlying mechanism remains unclear (1-3). Recent studies have revealed that the caspase family of cysteine proteases have been shown to play an important role in the regulation of several apoptotic processes. Thus, the present study investigated whether apoptosis induced by anticancer drugs is mediated by the activation of caspase cascade. NA cells, a squamous cell carcinoma cell line, were exposed to cisplatin (CDDP) or 5-fluorouracil (5-FU) with or without inhibitors of caspase 1, 3 and 8. Analysis of DNA fragmentation revealed that caspase inhibitors consistently inhibited DNA fragmentation induced by 5-FU. During the early stages of apoptosis, phosphatidylserine (PS) is translocated from the inner side of the plasma membrane to the cell surface. This PS externalization was markedly inhibited by treatment with caspase-8 inhibitor. These findings suggested that 5-FU induced apoptosis was mediated by the activation of a caspase cascade involving caspase 1, 3 and 8.