Silymarin inhibits cervical cancer cell through an increase of phosphatase and tensin homolog

Phytother Res. 2012 May;26(5):709-15. doi: 10.1002/ptr.3618. Epub 2011 Oct 20.

Abstract

Silymarin is an active constituent contained in the seeds of the milk thistle plant and is widely used as a hepatic protection agent due to its antioxidant-like activity. In the present study we evaluated the potential action of silymarin against cervical cancer and investigated its mechanism of action. Treatment of cervical cancer cells (C-33A) with silymarin resulted in a significant decrease in cell viability. Silymarin induced apoptosis through the modulation of Bcl-2 family proteins and activation of caspase 3. Silymarin also inhibited the phosphorylation of Akt with an increase in expression of phosphatase and tensin homolog (PTEN). We also observed that silymarin suppressed C-33A cell invasion and wound-healing migration in a concentration-dependent manner. Western-blot analysis showed that silymarin significantly inhibited the expression of matrix metalloproteinase-9 (MMP-9) in C-33A cells. Furthermore, we applied siRNA to lower the PTEN gene, which diminished the anticancer actions of silymarin. Taken together, these results show that silymarin has the potential to suppress the survival, migration and invasion of C-33A cancer cells; thus, it could be developed as a promising agent for the treatment of cervical cancer in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / drug effects
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Female
  • Genes, bcl-2 / drug effects
  • Humans
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase 9 / metabolism
  • PTEN Phosphohydrolase / drug effects
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering
  • Signal Transduction / drug effects*
  • Silymarin / pharmacology*
  • Uterine Cervical Neoplasms / drug therapy
  • Wound Healing / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • RNA, Small Interfering
  • Silymarin
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Caspase 3
  • Matrix Metalloproteinase 9