Gentisyl Alcohol Inhibits Proliferation and Induces Apoptosis via Mitochondrial Dysfunction and Regulation of MAPK and PI3K/AKT Pathways in Epithelial Ovarian Cancer Cells

Mar Drugs. 2019 Jun 3;17(6):331. doi: 10.3390/md17060331.

Abstract

Ovarian cancer is one of the prevalent gynecological cancers occurring in women. In particular, the efficiency of standard therapeutic methods decreases when recurrence and chemoresistance ensue. To assist standard anti-cancer agents in the cure of ovarian cancer, development and application of new compounds such as small molecules or natural products are required. Gentisyl alcohol is one of the secondary metabolites that can be obtained by purification from bacteria or fungi and is known to have antibacterial, antifungal, antiviral, and anti-cancer effects. In the present study, we verified the effect of gentisyl alcohol derived from marine Arthrinium sp. on suppressing proliferation and inducing apoptosis via DNA fragmentation in human ovarian cancers cells (ES2 and OV90 cells). We also confirmed that there was an accumulation of sub-G1 cells and a loss of mitochondrial membrane potential with calcium dysregulation in gentisyl alcohol-treated ovarian cancer cells. Moreover, gentisyl alcohol up-regulated signal transduction of MAPK and PI3K/AKT pathways. Collectively, our results demonstrated the possibility of gentisyl alcohol as a novel therapeutic agent for human ovarian cancer.

Keywords: calcium dysregulation; gentisyl alcohol; mitochondrial dysfunction; ovarian cancer.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Ascomycota / chemistry*
  • Ascomycota / metabolism
  • Benzyl Alcohols / chemistry
  • Benzyl Alcohols / isolation & purification
  • Benzyl Alcohols / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • MAP Kinase Signaling System / genetics
  • Mitochondria / drug effects*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Antineoplastic Agents
  • Benzyl Alcohols
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • 2,5-dihydroxybenzyl alcohol