Protocatechuic acid inhibits the growth of ovarian cancer cells by inducing apoptosis and autophagy

Phytother Res. 2018 Nov;32(11):2256-2263. doi: 10.1002/ptr.6163. Epub 2018 Jul 26.


Protocatechuic acid (PCA), present in many fruits and vegetables, exhibited various biological activities. Here, we provided evidence that it could be developed as a potential chemotherapeutic agent against human ovarian cancer. We found that PCA treatment significantly reduced the cell viability and colony formation of OVCAR-3, SKOV-3, and A2780 cells. OVCAR-3 cells were selected as a test model system for investigating molecular mechanism. PCA treatment induced cell cycle arrest in G2 /M phase, the activation of poly (ADP-ribose) polymerase (PARP) and caspase-3, the upregulation of Bax and downregulation of Bcl-2 in OVCAR-3 cells. We also observed that PCA treatment significantly caused upregulation of autophagy-related protein LC3-II and induced GFP-LC3 puncta formation. Furthermore, cotreatment with PCA and autophagy inhibitor attenuated the cytotoxicity induced by PCA in OVCAR-3 cells. Moreover, our results showed that PCA increased the intracellular levels of glutathione and decreased intracellular reactive oxygen species that might be related to the inhibition effect of PCA on OVCAR-3 cells. Our data revealed that PCA could modulate apoptosis and autophagy, suggesting the potential of PCA for chemoprevention and chemotherapy of ovarian cancer.

Keywords: apoptosis; autophagy; ovarian cancer; protocatechuic acid; reactive oxygen species.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Glutathione / metabolism
  • Humans
  • Hydroxybenzoates / pharmacology*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology*
  • Poly (ADP-Ribose) Polymerase-1 / metabolism
  • Reactive Oxygen Species / metabolism


  • Antineoplastic Agents
  • Hydroxybenzoates
  • Reactive Oxygen Species
  • protocatechuic acid
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • CASP3 protein, human
  • Caspase 3
  • Glutathione