Zeylenone inhibits proliferation and promotes apoptosis in ovarian carcinoma cells via Janus kinase 2 / signal transducers and activators of transcription 3 pathways

J Obstet Gynaecol Res. 2018 Aug;44(8):1451-1457. doi: 10.1111/jog.13690. Epub 2018 Jul 5.

Abstract

Aim: Ovarian cancer is the fifth common cancer in females. The aim of our study was to determine function of Zeylenone on cell viability and apoptosis of ovarian carcinoma SKOV3 cells.

Methods: Cell viability was measured by Cell counting kit-8 (CCK8) assay; Mitochondrial membrane potential (MMP) and apoptosis were detected by flow cytometry. The mRNA and protein levels of related factors were determined by Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively.

Results: Cell viability was decreased by Zeylenone in a dose-dependent manner. Zeylenone with concentrations of 2.5, 5 and 10 μmol/L was used to treat ovarian carcinoma SKOV3 cells for 24 h in the following study. The loss of MMP and apoptosis were both significantly increased by Zeylenone. The mRNA and protein levels of cytochrome c (cyto c) and apoptosis inducing factor (AIF) in cytosol were increased by Zeylenone. The mRNA and protein levels of Caspase-3, Fas, Fasl and Bax were increased; while the expression of Bcl-2 was decreased by Zeylenone. The expression of (Janus family of tyrosine kinase) p-JAK and signal transducer and activator of transcription (p-STAT) was decreased significantly by Zeylenone.

Conclusion: Zeylenone inhibited cell proliferation and promoted apoptosis in ovarian carcinoma cells. The JAK-STAT pathway was involved in this progress.

Keywords: JAK-STAT pathway; Zeylenone; apoptosis; mitochondria; ovarian carcinoma.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Cyclohexanes / pharmacology*
  • Dioxanes / pharmacology*
  • Female
  • Humans
  • Janus Kinase 2 / drug effects*
  • Membrane Potential, Mitochondrial / drug effects*
  • Ovarian Neoplasms / drug therapy*
  • Plant Extracts / pharmacology*
  • STAT3 Transcription Factor / drug effects*
  • Signal Transduction / drug effects*
  • Uvaria*

Substances

  • Cyclohexanes
  • Dioxanes
  • Plant Extracts
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • zeylenone
  • JAK2 protein, human
  • Janus Kinase 2