期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 31, 期 1, 页码 213-218出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2012.1176
关键词
dihydroartemisinin; breast cancer; proliferation; cell cycle; mitochondrial apoptosis; Bim; Bcl-2
资金
- National Natural Science Foundation of China [31270970]
- Science and Technology Project of Shandong, China [2008GG10002035, 2012G0021821]
- Science and Technology Project of Jinan, China [201202197]
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 mu M 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 Him 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.
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