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 ca ncel cells, the underlying mechanism remains unclear (1 - 3). Recent studie s have revealed that the caspase family of cysteine proteases have been sho wn to play an important role in the regulation of several apoptotic process es. Thus, the present study investigated whether apoptosis induced by antic ancer drugs is mediated by the activation of caspase cascade. NA cells, a s quamous cell carcinoma cell line, were exposed to cisplatin (CDDP) ol 5-flu orouracil (5-FU) with or. without inhibitors of caspase 1, 3 and 8 Analysis of DNA fragmentation revealed that caspase inhibitors consistently inhibit ed 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 inhibite d by treatment with caspase-8 inhibitor: These findings suggested that 5-FU induced apoptosis was mediated by the activation of a caspase cascade invo lving caspase 1, 3 and 8.