Corosolic acid induces cell cycle arrest and cell apoptosis in human retinoblastoma Y-79 cells via disruption of MELK-FoxM1 signaling

  • Authors:
    • Ke Wang
    • Xue Zhu
    • Yong Yao
    • Min Yang
    • Fanfan Zhou
    • Ling Zhu
  • View Affiliations

  • Published online on: March 28, 2018     https://doi.org/10.3892/or.2018.6339
  • Pages: 2777-2786
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Abstract

Retinoblastoma (Rb) is the most frequent primary intraocular tumor usually diagnosed in infants and children, and current therapy for such disease is still limited. Corosolic acid (CA), an ursane-type pentacyclic triterpene, has been assessed as a promising anticancer agent with little impact on untransformed cells. In the present study, we investigated the cytotoxic effect and underlying mechanism of CA on human retinoblastoma Y-79 cells. The viability of cells was verified by MTT assay. Cell cycle and apoptosis were evaluated by flow cytometric analysis. The expressions and activities of the related molecules were assessed by western blot analysis and luciferase assay. The results demonstrated that the treatment of CA dose-dependently induced cytotoxicity, cell cycle arrest and cell apoptosis in Y-79 cells. Furthermore, MELK-FoxM1 signaling was estimated to be involved in the cytotoxic effect of CA on Y-79 cells, and CA exerted its activity mainly through inhibition of the expression levels of MELK and FoxM1 as well as through suppression of the transcriptional activity of FoxM1 driven by itself or MELK. Our findings establish MELK-FoxM1 signaling as a promising therapeutic target for human retinoblastoma, and suggest the potential development of CA and its derivatives as novel drug candidates against this disease.

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June 2018
Volume 39 Issue 6

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

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APA
Wang, K., Zhu, X., Yao, Y., Yang, M., Zhou, F., & Zhu, L. (2018). Corosolic acid induces cell cycle arrest and cell apoptosis in human retinoblastoma Y-79 cells via disruption of MELK-FoxM1 signaling. Oncology Reports, 39, 2777-2786. https://doi.org/10.3892/or.2018.6339
MLA
Wang, K., Zhu, X., Yao, Y., Yang, M., Zhou, F., Zhu, L."Corosolic acid induces cell cycle arrest and cell apoptosis in human retinoblastoma Y-79 cells via disruption of MELK-FoxM1 signaling". Oncology Reports 39.6 (2018): 2777-2786.
Chicago
Wang, K., Zhu, X., Yao, Y., Yang, M., Zhou, F., Zhu, L."Corosolic acid induces cell cycle arrest and cell apoptosis in human retinoblastoma Y-79 cells via disruption of MELK-FoxM1 signaling". Oncology Reports 39, no. 6 (2018): 2777-2786. https://doi.org/10.3892/or.2018.6339