Euphol arrests breast cancer cells at the G1 phase through the modulation of cyclin D1, p21 and p27 expression

Mol Med Rep. 2013 Oct;8(4):1279-85. doi: 10.3892/mmr.2013.1650. Epub 2013 Aug 22.

Abstract

Euphorbia tirucalli is a long‑established treatment for a wide variety of cancers. However, the mechanism of its anticancer effect is yet to be elucidated. In the present study, we examined the anticancer effect of euphol, a tetracyclic triterpene alcohol isolated from the sap of Euphorbia tirucalli, in T47D human breast cancer cells. Following the treatment of cells with different doses of euphol for 24, 48 and 72 h, the cell proliferation, cell cycle, and mRNA and protein levels of cell cycle regulatory molecules were analyzed, respectively. Treatment of the cells with euphol resulted in decreased cell viability, which was accompanied by an accumulation of cells in the G1 phase. Further studies demonstrated that euphol treatment downregulated cyclin D1 expression and the hypophosphorylation of Rb. Furthermore, this effect was correlated with the downregulation of cyclin‑dependent kinase 2 (CDK2) expression and the upregulation of the CDK inhibitors p21 and p27. Reduced expression levels of cyclin A and B1 were also observed, corresponding to the decreased distribution of cells in the S and G2/M phases, respectively. These findings indicated that euphol is an active agent in Euphorbia tirucalli that exerts anticancer activity by arresting the cell cycle of cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Drug Screening Assays, Antitumor
  • Female
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lanosterol / analogs & derivatives*
  • Lanosterol / pharmacology
  • Retinoblastoma / metabolism
  • Transcription, Genetic / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • CCND1 protein, human
  • CDKN1A protein, human
  • CDKN1B protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • Lanosterol
  • euphol