Ursolic Acid Exhibits Potent Anticancer Effects in Human Metastatic Melanoma Cancer Cells (SK-MEL-24) via Apoptosis Induction, Inhibition of Cell Migration and Invasion, Cell Cycle Arrest, and Inhibition of Mitogen-Activated Protein Kinase (MAPK)/ERK Signaling Pathway

Background: Ursolic acid is an important bioactive triterpenoid that has been reported to be of tremendous pharmacolog-ical importance. However, the anticancer potential of ursolic acid has not been examined against metastatic melanoma cells. Therefore, in this study we examined the anticancer potential of ursolic acid and its mode of action. Material/Method: WST-1 and colony formation assays were used for cell viability assessment. Cell cycle analysis was performed by flow cytometry. Apoptosis was detected by AO/EB staining using fluorescence microscopy. Cell migration and invasion were assessed by Boyden chamber assay. Protein expression was checked by Western blotting. Results: The results revealed that ursolic acid exerts significant (p<0.01) growth-inhibitory effects on SK-MEL-24 cells. The IC50 of ursolic acid against SK-MEL-24 cells was 25 mu M. Our investigation of the underlying mechanism revealed that ursolic acid prompts apoptotic cell death of the SK-MEL-24 cells, which was linked with increased expression of Bax and Caspase 3 and 9, and decreased expression of BcI-2. Ursolic acid also halted the SKMEL-24 cells at GO/G1 phase of the cell cycle and also downregulated the expression of Cyclin B1 and Cdc25. Ursolic acid significantly (p<0.01) inhibited the migration and invasion of SK-MEL-2 cells, indicative of its anti-metastatic potential. Finally, ursolic acid inhibited the MAPK/ERK pathway by suppressing the expression of p-P38 and p-ERK. Conclusions: Ursolic acid appears to be a potent molecule for the treatment of melanoma.