title: Modulation of drug-resistant membrane and apoptosis proteins of breast cancer stem cells by targeting berberine liposomes.
abstract: The recurrence of breast cancer is associated with drug-resistance of cancer stem cells (CSCs), while overexpression of cell membrane ATP-binding cassette (ABC) transporters and resistance of mitochondrial apoptosis-related proteins are responsible for the drug-resistance of CSCs. The targeting berberine liposomes were developed to modulate the resistant membrane and mitochondrial proteins of breast CSCs for the treatment and prevention of breast cancer relapse. Evaluations were performed on human breast CSCs and CSC xenografts in nude mice. The targeting berberine liposomes were shown to cross the CSC membrane, inhibit ABC transporters (ABCC1, ABCC2, ABCC3, ABCG2) and selectively accumulate in the mitochondria. Furthermore, the pro-apoptotic protein Bax was activated while the anti-apoptotic protein Bcl-2 was inhibited resulting in opening of the mitochondrial permeability transition pores, release of cytochrome c, and activation of caspase-9/caspase-3 enzymes. Significant efficacy of the administrations in mice was observed, indicating that the targeting berberine liposomes are a potential therapy for the treatment and prevention of breast cancer relapse arising from CSCs.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.forename: Cheng-Xiang
authors.initials: CX
authors.lastname: Zhang
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Rui-Jun
authors.initials: RJ
authors.lastname: Ju
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Shi
authors.forename: Meng-Ge
authors.initials: MG
authors.lastname: Sun
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Zhao
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Mu
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Wan-Liang
authors.initials: WL
authors.lastname: Lu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001599:Berberine / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D003952:Diagnostic Imaging; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000633:toxicity; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000089762:Multidrug Resistance-Associated Protein 2; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: C000715087:ABCC2 protein, human; D018528:ATP-Binding Cassette Transporters; D051017:Apoptosis Regulatory Proteins; D008081:Liposomes; D008565:Membrane Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D001599:Berberine; D045304:Cytochromes c