Cytotoxic Effect of Clerosterol Isolated from Codium fragile on A2058 Human Melanoma Cells

The cytotoxic effects and mechanism of action of clerosterol, isolated from the marine alga Codium fragile, were investigated in A2058 human melanoma cells. Clerosterol inhibited the growth of A2058 cells with an IC50 of 150 mu M and induced apoptotic cell death, as evidenced by DNA fragmentation, an increase in the number of sub-G(1) hypodiploid cells and the presence of apoptotic bodies. Clerosterol treatment caused the loss of mitochondrial membrane potential. Alterations in the expression of apoptosis-associated proteins in response to clerosterol treatment included upregulation of Bax, downregulation of Bcl-2 and activation of caspases 3 and 9. The pan-caspase inhibitor treatment attenuated the expression of the active form of caspases and cell death induced by clerosterol. The present results show that clerosterol exerts its cytotoxic effect in A2058 human melanoma cells by caspases-dependent apoptosis.