Class of 2013 Abstract / Specific Aims: To determine if melanoma cells are more vulnerable to Amodiaquine (AQ) or Lumefantrine (LF)-based artemisinin combination therapy compared to artemisinin monotherapy. Methods: Tested anti-malarials in vitro for anti-melanoma activity, which contained 100,000 of the A375 human metastatic melanoma cells that were repeatedly treated independently three times. Main Results: Dihydroartemisinin (DHA) monotherapy induced significant cell death in melanoma cells. However, artemisinin combination therapy (ACT) did not enhance DHA-induced cell death. AQ protected against DHA-induced cell death causing morphological changes detected by electron microscopy. As for LF, it did not affect DHA-induced cell death. Conclusion: The results demonstrated that ACT does not display enhanced anti-melanoma activity compared to artemisinin monotherapy. It suggests that AQ may have anti-oxidant properties, but would need to be explored further in the context of anti-oxidant cyto-protection.