Cucurbitacin B induces autophagy and apoptosis by suppressing CIP2A/PP2A/mTORC1 signaling axis in human cisplatin resistant gastric cancer cells

  • Authors:
    • Xuewen Liu
    • Chao Duan
    • Juanli Ji
    • Te Zhang
    • Xiaoning Yuan
    • Yunfei Zhang
    • Wenjing Ma
    • Jingyuan Yang
    • Linsen Yang
    • Zhiguo Jiang
    • Huiliang Yu
    • Ying Liu
  • View Affiliations

  • Published online on: May 18, 2017     https://doi.org/10.3892/or.2017.5648
  • Pages: 271-278
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Abstract

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of tumors including gastric cancer (GC). Mammalian target of rapamycin complex 1 (mTORC1) over-activation is detected in GC and many other cancers. Previous study found that CIP2A/mTORC1 controls cell growth and autophagy through direct association. CIP2A plays an ‘oncogenic nexus’ in several cancer types to participate in the tumorigenic transformation and chemoresistance. In the present study, we investigated whether Cucurbitacin B (CuB), a natural compound found in Cucurbitaceae, can be used in cisplatin (DDP)-resistant human GC cell line SGC7901/DDP. Results demonstrated that CuB treatment significantly suppressed SGC7901/DDP cell proliferation, induced caspase-dependent apoptosis, and autophagy. The activation of autophagy was mediated through CuB-induced inhibition of mTORC1. Furthermore, CuB inhibited mTORC1 via the activation of protein phosphatase 2A (PP2A) which is mediated by CIP2A inhibition. These findings indicated that CuB can inhibit the proliferation, induce caspase-dependent apoptosis, and autophagy of SGC7901/DDP cells by suppressing CIP2A/PP2A/mTORC1 signaling axis. Thus, CuB may be a novel effective candidate to treat DDP-resistant human GC cells.
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July-2017
Volume 38 Issue 1

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

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Spandidos Publications style
Liu X, Duan C, Ji J, Zhang T, Yuan X, Zhang Y, Ma W, Yang J, Yang L, Jiang Z, Jiang Z, et al: Cucurbitacin B induces autophagy and apoptosis by suppressing CIP2A/PP2A/mTORC1 signaling axis in human cisplatin resistant gastric cancer cells. Oncol Rep 38: 271-278, 2017
APA
Liu, X., Duan, C., Ji, J., Zhang, T., Yuan, X., Zhang, Y. ... Liu, Y. (2017). Cucurbitacin B induces autophagy and apoptosis by suppressing CIP2A/PP2A/mTORC1 signaling axis in human cisplatin resistant gastric cancer cells. Oncology Reports, 38, 271-278. https://doi.org/10.3892/or.2017.5648
MLA
Liu, X., Duan, C., Ji, J., Zhang, T., Yuan, X., Zhang, Y., Ma, W., Yang, J., Yang, L., Jiang, Z., Yu, H., Liu, Y."Cucurbitacin B induces autophagy and apoptosis by suppressing CIP2A/PP2A/mTORC1 signaling axis in human cisplatin resistant gastric cancer cells". Oncology Reports 38.1 (2017): 271-278.
Chicago
Liu, X., Duan, C., Ji, J., Zhang, T., Yuan, X., Zhang, Y., Ma, W., Yang, J., Yang, L., Jiang, Z., Yu, H., Liu, Y."Cucurbitacin B induces autophagy and apoptosis by suppressing CIP2A/PP2A/mTORC1 signaling axis in human cisplatin resistant gastric cancer cells". Oncology Reports 38, no. 1 (2017): 271-278. https://doi.org/10.3892/or.2017.5648