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

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 G(2)/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.