Ursolic acid induced apoptotic cell death following activation of caspases in isolated human melanoma cells

Ursolic acid (UA) is plentifully present in fruits, foods, and medicinal plants, and has anti-cancer activity on many cancer cell lines. However, the effects of UA on some melanoma cells and the mechanisms of action have not been reported. The effect of UA on isolated human melanoma and fibroblast cell lines has been investigated using the MTT assay, and cell death was determined using Annexin-V/PI staining. To explore whether the activation of caspases was required for apoptosis induction, cells were treated with pan-caspase inhibitor and UA. Changes in apoptosis pattern were analyzed by flow cytometry. Activation of caspases was detected by western blot analysis. A significant concentration-dependent suppression of cell proliferation was seen after 24 and 48h in the presence of UA. Apoptosis was considerably increased by UA, indicated by enhancement of an Annexin-V positive population and a sub-G1 peak. UA induced proteolytic processing of caspase-3. The results confirm the anti-cancer properties of UA on cultured human melanoma cells, possibly mediated through the induction of apoptosis following activation of caspases.