Gambogenic acid induces proteasomal degradation of CIP2A and sensitizes hepatocellular carcinoma to anticancer agents

  • Authors:
    • Xian‑Jun Yu
    • Qun Zhao
    • Xuan‑Bin Wang
    • Jing‑Xuan Zhang
    • Xiao‑Bo Wang
  • View Affiliations

  • Published online on: October 20, 2016     https://doi.org/10.3892/or.2016.5188
  • Pages: 3611-3618
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Abstract

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is overexpressed in many human malignancies. It regulates phosphorylated AKT and stabilizes c‑Myc in cell proliferation and tumor formation, suggesting that CIP2A plays an essential role in the development of cancer. In the present study, we report that a natural compound, gambogenic acid (GEA), induced the degradation of CIP2A via the ubiquitin‑proteasome pathway. Interestingly, the combination of GEA and proteasome inhibitors potentiated the accumulation of ubiquitinated CIP2A and aggresome formation. In addition, GEA exhibited an inhibitory effect on cell proliferation and CIP2A‑downstream signaling molecules (c‑Myc and pAKT). Furthermore, GEA and CIP2A silencing enhanced the chemosensitivity of hepatocellular carcinoma cells to anticancer agents, suggesting that a combination of a CIP2A inhibitor and anticancer agents could be a valuable clinical therapeutic strategy. These results indicate that GEA is a CIP2A inhibitor that interferes with the ubiquitination and destabilization of CIP2A, providing a promising strategy to enhance the combinational therapy for hepatocellular carcinoma.
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December-2016
Volume 36 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Yu XJ, Zhao Q, Wang XB, Zhang JX and Wang XB: Gambogenic acid induces proteasomal degradation of CIP2A and sensitizes hepatocellular carcinoma to anticancer agents. Oncol Rep 36: 3611-3618, 2016
APA
Yu, X., Zhao, Q., Wang, X., Zhang, J., & Wang, X. (2016). Gambogenic acid induces proteasomal degradation of CIP2A and sensitizes hepatocellular carcinoma to anticancer agents. Oncology Reports, 36, 3611-3618. https://doi.org/10.3892/or.2016.5188
MLA
Yu, X., Zhao, Q., Wang, X., Zhang, J., Wang, X."Gambogenic acid induces proteasomal degradation of CIP2A and sensitizes hepatocellular carcinoma to anticancer agents". Oncology Reports 36.6 (2016): 3611-3618.
Chicago
Yu, X., Zhao, Q., Wang, X., Zhang, J., Wang, X."Gambogenic acid induces proteasomal degradation of CIP2A and sensitizes hepatocellular carcinoma to anticancer agents". Oncology Reports 36, no. 6 (2016): 3611-3618. https://doi.org/10.3892/or.2016.5188