Obacunone regulates ferroptosis in ovarian cancer through the Akt/p53 pathway

Ovarian cancer is characterized by a high rate of recurrence and a poor prognosis. Ferroptosis, a programmed cell death that is dependent on iron and lipid peroxidation, has emerged as a novel therapeutic target in recent years. This study investigated the effects of Obacunone, a naturally occurring compound present in citrus fruits, on the induction of ferroptosis in ovarian cancer via the Akt/p53 signaling pathway. SKOV3 and OVCAR3 ovarian cancer cell lines were utilized in vitro, while a BALB/c nude mouse model was employed for in vivo experiments. Cell proliferation was assessed utilizing the CCK-8 assay and EDU incorporation. The western blot technique was employed to assess the expression levels of proteins associated with the Akt/p53 signaling pathway. The ferroptosis inhibitor Fer-1 and the Akt activator SC79 were utilized to investigate the potential mechanism of action of Obacunone. Obacunone significantly inhibited the proliferation of ovarian cancer cells and induced ferroptosis, as evidenced by increased intracellular iron content, elevated lipid peroxidation levels, and abnormal mitochondrial morphology. Obacunone also decreased GSH levels, inhibited GPX4 expression and up-regulated ACSL4, as well as reduced Akt phosphorylation and enhanced p53 expression. In vivo experiments showed that Obacunone effectively inhibited tumor growth. Obacunone exhibits potential therapeutic significance through the modulation of the Akt/p53 signaling pathway, which may induce ferroptosis and inhibit the proliferation of ovarian cancer cells.