Pentagalloylglucose induces ovarian cancer cell senescence via inhibition of AKT signaling

This research aimed to investigate the therapeutic potential of pentagalloylglucose (PGG) in ovarian cancer and elucidate its underlying molecular mechanisms. The IC 50 of PGG on A2780, Caov-3, and SK-OV-3 cells was determined using CCK-8 kits. The effects of PGG on cell proliferation, cell cycle, and senescence were assessed by colony formation, EdU staining, flow cytometry, SA-β-gal staining, and γH2AX immunofluorescence. Bioinformatics analysis and molecular docking were employed to predict potential targets of PGG, which were subsequently validated through in vitro and in vivo approaches. A xenograft mouse model was employed to evaluate the anti-tumor activity of PGG in vivo. PGG exhibited cytotoxicity against ovarian cancer cells with IC 50 values of 8.41 µM for A2780, 22.84 µM for Caov-3, and 44.27 µM for SK-OV-3 cells. PGG dose-dependently inhibited proliferation, induced G0/G1 phase arrest, enhanced SA-β-gal and γH2AX positivity, upregulated p16 and p21, and downregulated p-Rb. AKT2 was identified as one of the potential targets. PGG docked into AKT2, promoted its ubiquitination and proteasomal degradation, and inhibited AKT/mTOR signaling. Overexpression of AKT2 reversed PGG-induced growth suppression and senescence promotion. Moreover, PGG effectively inhibited tumor growth in vivo, promoted tumor cell senescence, and suppressed the AKT/mTOR pathway. PGG exerts cytotoxic effects and induces senescence-associated cell cycle arrest in ovarian cancer cells. AKT2 may serve as a key target mediating its anti-ovarian cancer activity. Not applicable.