title: 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.
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, PR China. haitingmao@yahoo.com
authors.forename: Haiting
authors.initials: H
authors.lastname: Mao
authors.forename: Hongtao
authors.initials: H
authors.lastname: Gu
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
authors.forename: Jintang
authors.initials: J
authors.lastname: Sun
authors.forename: Bingfeng
authors.initials: B
authors.lastname: Song
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Gao
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Shao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D037621:Artemisinins / Q000494:pharmacology*; D000072224:Bcl-2-Like Protein 11; D001943:Breast Neoplasms / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D037621:Artemisinins; C494826:BAX protein, human; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051028:bcl-2-Associated X Protein; C039060:artenimol; D045304:Cytochromes c; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9