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

Dihydroartemisinin (DHA), a semi-synthetic derivative and active metaboliteof artemisinin, has been shown to have profound anticancer potential in additionto its strong anti-malarial activity. The purpose of the present study was tothoroughly investigate the anti-neoplastic effects induced by DHA and to providea molecular basis for the use of DHA in the treatment of breast cancer. Our resultsdemonstrated that DHA could significantly inhibit the cell proliferation of breastcancer in a dose- and time-dependent manner that was associated with induced apoptosisand 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 frommitochondria into the cytosol. In addition, the apoptotic action of DHA was associatedwith the increased expression of the pro-apoptotic gene Bim and a decreased expressionof the anti-apoptotic gene Bcl-2. Therefore, the mitochondrial pathway is involvedin the apoptosis of breast cancer cells induced by DHA and the imbalance of theBim/Bcl-2 interaction may promote the beneficial effect against breast cancercells. Overall, our study provides the scientific rationale for the clinical usageof DHA for breast cancer.