title: Cucurbitacin B reverses multidrug resistance by targeting CIP2A to reactivate protein phosphatase 2A in MCF-7/adriamycin cells.
abstract: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in various tumors. A previous study found that CIP2A expression is associated with doxorubicin (Dox) resistance. In the present study, we investigated whether cucurbitacin B (CuB), a natural anticancer compound found in Cucurbitaceae, reversed multidrug resistance (MDR) and downregulated CIP2A expression in MCF-7/Adriamycin (MCF-7/Adr) cells, a human breast multidrug-resistant cancer cell line. CuB treatment significantly suppressed MCF-7/Adr cell proliferation, and reversed Dox resistance. CuB treatment also induced caspase-dependent apoptosis, decreased phosphorylation of Akt (pAkt). The suppression of pAkt was mediated through CuB-induced activation of protein phosphatase 2A (PP2A). Furthermore, CuB activated PP2A through the suppression of CIP2A. Silencing CIP2A enhanced CuB-induced growth inhibition, apoptosis and MDR inhibition in MCF-7/Adr cells. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A promotes the reversal of MDR induced by CuB.
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Fen
authors.initials: F
authors.lastname: Cai
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Duan
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001324:Autoantigens / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019662:Cucurbitaceae / Q000737:chemistry; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001324:Autoantigens; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D014315:Triterpenes; C041246:cucurbitacin B; D004317:Doxorubicin; D051057:Proto-Oncogene Proteins c-akt; D054648:Protein Phosphatase 2; D020169:Caspases