Silibinin down-regulates expression of secreted phospholipase A2 enzymes in cancer cells

Anticancer Res. 2014 Apr;34(4):1723-9.

Abstract

Background: Silibinin, a naturally-occurring flavonoid produced by milk thistle, possesses antioxidant, anti-inflammatory and cancer-preventive activities. In the current study, we examined the effects of silibinin on the expression of secreted phospholipase A2 (sPLA2) enzymes, especially those of group IIA (hGIIA), which play a crucial role in inflammation and carcinogenesis.

Materials and methods: The effects of silibinin on sPLA2 expressions in human HepG2 hepatoma and PC-3 prostate cancer cells were analyzed using quantitative reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay technique.

Results: Silibinin inhibited the expression of hGIIA in unstimulated and cytokine-primed HepG2 and PC-3 cells. The mRNA levels of sPLA2 of groups IB, III and V were also significantly decreased by silibinin. Analyses of transcription factor activation suggest that nuclear factor-κB, but not specificity protein 1 (SP1) is implicated in the silibinin-mediated down-regulation of hGIIA.

Conclusion: Silibinin exhibits inhibitory effects on basal and cytokine-induced expression of sPLA2s in cancer cells and therefore, may have the potential to protect against up-regulation of hGIIA and other sPLA2 isoforms during inflammation and cancer.

Keywords: Secreted phospholipase A2; cancer cells; signaling pathways; silibinin.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Phospholipases A2, Secretory / genetics*
  • Phospholipases A2, Secretory / metabolism
  • RNA Isoforms
  • Signal Transduction / drug effects
  • Silybin
  • Silymarin / pharmacology*
  • Sp1 Transcription Factor / metabolism
  • Tumor Stem Cell Assay

Substances

  • Antineoplastic Agents
  • RNA Isoforms
  • Silymarin
  • Sp1 Transcription Factor
  • Silybin
  • Phospholipases A2, Secretory