title: Cyclosporine A inhibits breast cancer cell growth by downregulating             the expression of pyruvate kinase subtype M2.
abstract: The high proliferative rate of tumor cells leads to metabolic needs distinct             from those of their normal counterparts. An embryonic- and tumor-specific isoform             of the enzyme pyruvate kinase M2 (PKM2) is overexpressed in cancer cells to increase             the use of glycolytic intermediates for macromolecular biosynthesis and tumor             growth. We report that Cyclosporin A (CsA) can regulate the expression and activity             of PKM2 in breast cancer cell lines MCF-7, MDA-MB-435 and MDA-MB-231. PKM2 was             found to be highly expressed in the three breast cancer cell lines compared to             normal primary breast cells. Treatment with CsA inhibited the viability of breast             cancer cells in a time- and dose-dependent manner. CsA significantly downregulated             the expression of PKM2 in breast cancer cells and decreased adenosine triphosphate             (ATP) synthesis, which induced cancer cells to undergo necrosis. Furthermore,             the growth suppression effect of CsA was impaired in MCF-7 cells when they were             transfected with the PKM2 overexpression plasmid, suggesting that CsA was an effective             inhibitor of PKM2-dependent proliferation of breast cancer cells. These results             may provide new insights into the mechanism of CsA in cancer therapy.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine,                     Hangzhou 310058, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.forename: Baoming
authors.initials: B
authors.lastname: He
authors.forename: Lihua
authors.initials: L
authors.lastname: Lai
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Qingming
authors.initials: Q
authors.lastname: Guo
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D011770:Pyruvate Kinase / Q000235:genetics* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D016572:Cyclosporine; D011770:Pyruvate Kinase