Involvement of the mitochondrial pathway and Bim/Bcl-2 balance in dihydroartemisinin-induced apoptosis in human breast cancer in vitro

Abstract

Dihydroartemisinin (DHA), a semi-synthetic derivative and active metabolite of artemisinin, has been shown to have profound anticancer potential in addition to its strong anti-malarial activity. The purpose of the present study was to thoroughly investigate the anti-neoplastic effects induced by DHA and to provide a molecular basis for the use of DHA in the treatment of breast cancer. Our results demonstrated that DHA could significantly inhibit the cell proliferation of breast cancer in a dose- and time-dependent manner that was associated with induced apoptosis and G0/G1 cell cycle arrest, and the half maximal inhibitory concentrations (IC50) of DHA treatment were 60.03, 33.86 and 17.18 μM for 24, 48 and 72 h, respectively. Moreover, the DHA treatment dramatically increased the protein expression of caspase-8, cleaved caspase-9, activated Bid and induced the release of cytochrome c from mitochondria into the cytosol. In addition, the apoptotic action of DHA was associated with the increased expression of the pro-apoptotic gene Bim and a decreased expression of the anti-apoptotic gene Bcl-2. Therefore, the mitochondrial pathway is involved in the apoptosis of breast cancer cells induced by DHA and the imbalance of the Bim/Bcl-2 interaction may promote the beneficial effect against breast cancer cells. Overall, our study provides the scientific rationale for the clinical usage of DHA for breast cancer.