Cyclosporine A inhibits breast cancer cell growth by downregulating the expression of pyruvate kinase subtype M2

Jiang,Kai; He,Baoming; Lai,Lihua; Chen,Qingyun; Liu,Yang; Guo,Qingming; Wang,Qingqing

doi:10.3892/ijmm.2012.989

Cyclosporine A inhibits breast cancer cell growth by downregulating the expression of pyruvate kinase subtype M2

Authors:
- Kai Jiang
- Baoming He
- Lihua Lai
- Qingyun Chen
- Yang Liu
- Qingming Guo
- Qingqing Wang
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Affiliations: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China, Department of Nuclear Medicine, 309 Hospital of PLA, Beijing 100091, P.R. China
Published online on: May 9, 2012 https://doi.org/10.3892/ijmm.2012.989
Pages: 302-308

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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.

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