Caspase-2 activation induced by cisplatin on a human oral squamous cell carcinoma cell line

Abstract

Cisplatin (CDDP) is a potent DNA-damaging anticancer agent that induces cytotoxic action by induction of apoptosis. However, its underlying molecular mechanisms remain to be elucidated. We examined the activation of caspase-2, which is involved in the induction of apoptosis by CDDP, in relation to Bax translocation and the interaction of cytochrome c release from mitochondria. The human oral squamous cell carcinoma cell line (HSC-4) was employed in this study.
     We found that treatment of HSC-4 cells with CDDP decreased cell viability in a dose-dependent manner, and induced apoptosis. One of the apoptosome molecules, cytochrome c, was significantly augmented in the cytoplasm by CDDP treatment. Activation of caspase-2, -3 and -9 was detected after treatment with CDDP. Furthermore, apoptosis was blocked when HSC-4 cells that had been treated with CDDP were co-treated with caspase inhibitors such as Z-DEVD-FMK, Z-VDVAD-FMK and Z-LEHD-AFC. In addition, caspase-2 inhibitor decreased cytochorome c release and delayed Bax translocation into mitochondria.
     Our results suggest that activation of caspase-2 occurs upstream of the mitochondrial pathway in CDDP-induced apoptosis, and regulates both cytochrome c release and Bax translocation.