Arsenic Trioxide Induces Apoptosis of Human Uveal Melanoma Cells via Caspase Activation

Abstract

Uveal melanoma is the most common primary intraocular malignancy in adults and it is highly resistant to most chemotherapeutic drugs. Arsenic trioxide (ATO) has been showed to trigger apoptosis in some solid tumor cells. In present study we investigated the cytotoxic effects of ATO on human M17 uveal melanoma cell line, and explored the underlying intracellular molecular mechanisms of ATO. Using the MTT assay, we found that ATO selectively inhibited growth of uveal melanoma cells in a dose-dependent manner, and the IC50 values at 48 hr after ATO treated were 1.98±0.23 and 122.4±4.44 (g/ml for M17 and human normal fibroblast cells, respectively. After treated with 1 and 3 (g/ml of ATO for 24 hr, the apoptotic cells were increased dramatically by 18.2-and 14.5-fold in M17 cells. Furthermore, ATO treatment resulted in 4.8-, 2.8-and 4.8-fold increase in the activity of caspase-3, -8 and -9, respectively. It also increased the cytochrome c level by 2.1-fold in uveal melanoma cell. Taken together, these results suggest that ATO has a selective cytotoxic effect on human uveal melanoma cells through the caspase-activation cell apoptotic pathway.