Abstract
Artesunate is a chemical derivative of Artemisinin that was reported to combat cancer. In this study, screening of eleven cancer cell lines from six tissue origins demonstrated that Artesunate effectively inhibited proliferation of liver cancer cell lines in vitro. Using HepG2 cells as a model, Artesunate induced Erk1/2 phosphorylation and DAPK1 dephosphorylation, triggering apoptosis. Complementation with U0126 revoked Erk1/2-DAPK1 phosphorylation and exerted modest proliferative advantage at early time points, but eventually did not rescue HepG2 cells from death. U0126 induced multiploid formation independent of Artesunate, resulting in cell cycle arrest within 24 h post-treatment. However, Artesunate was ineffective in inhibiting tumor growth in vivo. Prevailing evidence manifested that tissue architecture did not confer to Artesunate inefficacy in vivo. Hence, we hypothesized that the rapid blood clearance of Artesunate attributed to its inefficacy in vivo. Given that Artesunate had no apparent impact on mouse body weight and blood biochemistry, Artesunate provided an option for chemotherapy with mild side effects, if smart design of drug delivery might improve its distribution in vivo.