Comparative Studies on the Antitumor Effect of Artemisinin, Artesunate and Artemether Against StageII Breast Cancer in Animal Model

Cancer is a widespread disease in which regulatory mechanisms of cell growth and proliferation has led into failure and results in continuous cell reproduction. Nowadays, breast cancer is one of the most common diseases, especially among women. In recent years anti-cancer effects of Artemisinin has taken into consideration. Artemisinin and its two derivatives, Artesunate and Artemether, each have special anti-cancer properties. In our hypothesis using these drugs as a combination may reinforces their antitumor features. At first 4T1 cells were cultured and then were treated with 15-135 microgram of Artemisinin, Artesunate, Artemether and their combination form for 24 and 48 hours and eventually MTT assay was performed to evaluate the cytotoxic effect of drugs. Then we tested the in vivo antitumor effect and cytokine shifting of these drugs in 6 groups of mice.

In MTT assay we observed that all drugs kill 4T1 cell line in a dose-dependent pattern while have no significant cytotoxic effect on normal cells. The combination form of drugs killed 50% of cancerous cells at a concentration of 75 microgram, while Artesunate and Artemether had the same cytotoxic effect at a concentration of 90 microgram and Artemisinin at a concentration of 105 microgram. All these drugs and the combination form could increase the INF-γ level in mice but only Artemisinin and combination group could slow down the tumor growth compared to the control group. No substantial difference was observed between Artesunate and Artemether and control group (P<0/05). Although all drugs specially combination form showed considerable and specific cytotoxic effects in vitro, but only Artemisinin and combination form could slow down the tumor growth in vivo. However, still more detailed information is required to decide about the combination form of drugs and its antitumor properties.

Keywords: Artemisinin, Artesunate, Artemether, combination therapy, breast cancer, 4T1 cell line.