Background: The objective of the present study was to investigate how oxidative status influences the effectiveness of cytotoxicity of artemisinin towards cancer cells. It is hypothesized that antioxidants would reduce, whereas pro-oxidants would enhance, cytotoxicity. Materials and Methods: Molt-4 human leukemia cells were incubated with vitamins C, E, D-3, dexamethasone, or hydrogen peroxide alone or in combination with dihydroartemisinin (DHA). Concentrations of these compounds studied were similar to those achievable by oral administration. Viable cell counts were performed before (0 h) and at, 24 and 48 h after treatment. Results: Vitamin C, vitamin D3, dexamethasone, and H2O2 caused significant Molt-4 cell death. Vitamin E caused an increase in Molt-4 cell growth. Vitamin C and vitamin D3 significantly interacted with DHA at the 48-h time point and with H2O2 at both 24-h and 48-h time points. Conclusion: Cellular oxidative status could alter the potency of artemisinin in killing cancer cells.

Artemisinin has been shown to be an effective antimalarial and anticancer compound. Dimers of artemisinin have been synthesized and shown to be potent antimalarials compared with monomers. In the present study, we investigated the effect of two artemisinin dimers (dimer-alcohol and dimer-hydrazone) on rat mammary adenocarcinoma cells (MTLn3) in vitro and in vivo compared with that of the artemisinin monomer dihydroartemisinin (DHA). We found that the dimers are considerably more potent than DHA in killing MTLn3 cells in vitro and suppressing the growth of MTLn3 breast tumors in vivo.