Induction of Apoptosis in Human Breast Cancer MCF-7 Cells by a Semi-Synthetic Derivative of Artemisinin: A Caspase-Related Mechanism

摘要

Background: Artesunate has recently been used in some pharmacological preparation to induce tumor cell apoptosis. The drug is a semi-synthetic derivative of artemisinin, traditionally used for its antimalarial. However, up to now, its anticancer mechanism against different types of tumors is not known. Objectives: The most important purposes of the present research was firstly investigating induction of apoptosis on human breast cancer MCF-7 cells by the drug and, in the second place, introducing its possible mechanism of action. Materials and Methods: The MTT assay was used to investigate the inhibitory effect of artesunate on growth of breast cancer MCF-7 cells. For this aim, different concentrations of artesunate were used to treat the cells and flow cytometry assay was done followed by annexin V-FITC/PI staining. The activities of caspase-3, -8 and -9 were then determined by relative assay kits. Results: Based on the results from MTT assay, it was found that artesunate could significantly inhibit the growth of MCF-7 cells in a dose- and time-dependent manner. On the other hand, the flow cytometry findings showed that the anti-proliferative activity of artesunate on MCF-7 cells is due to apoptosis. Besides, caspase colorimetric assays revealed a significant rise in cellular levels of the initiators (caspase-8 and -9) and effector (caspase-3) in the cells treated by artesunate. Conclusions:According to our results, it could be concluded that artesunate could inhibit the growth of MCF-7 breast cancer cells through induction of apoptosis by intrinsic and extrinsic caspase-dependent pathways. Therefore, we claim that artesunate could be introduced as a suitable candidate for the treatment of the breast cancer.