Anticancer and chemo-sensitizing effects of annonacin via p53-mediated DNA damage in ovarian cancer

Ovarian cancer (OC) is a highly lethal malignancy in women, often diagnosed at advanced stages. Carboplatin is the primary chemotherapy drug used clinically; however, most patients experience relapse and develop drug resistance after initial treatment, underscoring the urgent need for novel therapeutic strategies. This study investigated the anti-cancer activity and chemo-sensitizing effects of annonacin, an active compound in the fruit extract of Asimina triloba, as well as its underlying mechanisms in OC. Our results demonstrated that annonacin significantly inhibited OC cell viability, DNA replication, and proliferation, while inducing cell cycle arrest and senescence. Additionally, annonacin reduced OC cell-matrix adhesion and suppressed cell migration and invasion. Furthermore, annonacin enhanced the anti-OC efficacy of carboplatin by inducing substantial DNA damage, exhibiting a synergistic anticancer effect. Mechanistically, annonacin exerted potent anti-cancer and anti-migration activities through the p53 signaling pathway-mediated DNA damage response. When combined with carboplatin, this effect was further amplified. In vivo studies showed that annonacin effectively inhibited tumor growth in mice, and its combination with carboplatin demonstrated superior tumor-suppressive capabilities. Acute toxicity assays confirmed that annonacin possesses good biological safety in vivo. Collectively, these findings suggest that annonacin is a promising chemotherapeutic agent for OC treatment and highlight the potential of its combination with carboplatin to improve therapeutic outcomes in OC.