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

Oncol Rep. 2018 Jun;39(6):2777-2786. doi: 10.3892/or.2018.6339. Epub 2018 Mar 28.


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.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Forkhead Box Protein M1 / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Protein Serine-Threonine Kinases / metabolism*
  • Retinoblastoma / drug therapy
  • Retinoblastoma / metabolism*
  • Signal Transduction / drug effects
  • Triterpenes / pharmacology*


  • Antineoplastic Agents, Phytogenic
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Triterpenes
  • corosolic acid
  • MELK protein, human
  • Protein Serine-Threonine Kinases