Objective: To investigate the effects and mechanisms of arsenic trioxide (ATO) on human choroidal melanoma cell line OCM-1.
Methods: OCM-1 cells were cultured with 0.75 to 24.00 micromol/L arsenic trioxide for various durations, then cell viability was measured by MTT assay. The cell necrosis and apoptosis rates were observed by flow cytometry. The morphological changes of the cells were examined by electron microscopy. Glutathione peroxidase (GSH-Px) activities were tested. Mitochondrial membrane potential (MMP) was detected by confocal microscopy.
Results: Growth of OCM-1 cells was inhibited by ATO at concentrations of (1.5 to 24.0) micromol/L. However, there was no effect of 0.75 micromol/L ATO on the growth of OCM-1 cells. The inhibition showed both dose and time dependent effects (P < 0.05). The IC(50) was 16.8 micromol/L at 24 h. Flow cytometry analysis showed a positive correlation between the rate of cell necrosis and apoptosis and the concentration of ATO. The cell necrosis rates were higher than the cell apoptosis rates at various concentrations of ATO. OCM-1 cells cultured with ATO showed the classic morphologic characteristics of necrosis and apoptosis. GSH-Px activities and MMP decreased in a dose dependent manner.
Conclusion: ATO inhibits the growth of OCM-1 cells. The mechanism of this effect is that ATO inhibits the GSH-Px activities, decreases the MMP and impairs mitochondrial energy synthesis, which induces necrosis and apoptosis of human choroidal melanoma COM-1 cells eventually.