Caspase-independent autophagic cytotoxicity in etoposide-treated CaSki cervical carcinoma cells

We studied the in vitro mechanism of etoposide-induced cell death in cervical cancer cells. Etoposide is cytotoxic to these cells, causing cell death by both apoptosis and autophagy, which has recently been described as a possible mechanism for nonapoptotic cell death. Electron microscopy revealed that autophagosomes/autolysosomes exhibited an autophagic appearance in the presence of etoposide. When autophagy was blocked by inhibitors of autophagy, including 3-methyladenine, both the expression of beclin 1 protein and the antitumor effect of etoposide were suppressed. Benzyloxycarbonyl-Val-Ala-Asp- fluoromethyl ketone, a pan-caspase inhibitor, reduced etoposide-induced cytotoxicity in CaSki cells. Hence, autophagy and apoptosis likely occur concurrently in etoposide-treated cervical cancer cells.