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Oncol Rep. 2016 Aug;36(2):1180-6. doi: 10.3892/or.2016.4892. Epub 2016 Jun 22.

Cucurbitacin B reverses multidrug resistance by targeting CIP2A to reactivate protein phosphatase 2A in MCF-7/adriamycin cells.

Author information

1
Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.

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.

PMID:
27350399
DOI:
10.3892/or.2016.4892
[Indexed for MEDLINE]

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