Cinnamaldehyde suppresses ovarian cancer progression by activating ROS-mediated apoptosis and mitophagy

Cinnamaldehyde (CA), a natural bioactive compound derived from Cinnamomum species, has demonstrated broad-spectrum antitumor activity. However, its therapeutic potential and precise mechanisms in ovarian cancer (OC) remain incompletely elucidated. In this study, we systematically investigated the inhibitory effects of CA on OC and the underlying molecular mechanisms through both in vitro and in vivo approaches. In vitro experiments demonstrated that CA significantly induces reactive oxygen species (ROS) accumulation in OC cells, activates mitochondria-mediated apoptosis, and induces mitochondrial autophagy via the AMPK/ULK1/Beclin1 signaling axis. These synergistic effects collectively lead to significant suppression of OC cell proliferation. In a murine xenograft model of OC, CA administration substantially inhibited the growth of heterotransplanted tumors. Further in vivo analyses revealed a significant increase in the number of apoptotic cells and upregulation of the expression of the autophagy markers LC3B, PINK1, and Parkin in tumor tissues. Concurrently, the expression of the autophagic substrate p62 and the mitochondrial membrane protein TOMM20 decreased. These findings consistently corroborated the cellular mechanisms observed in vitro. This study provides the first evidence that CA suppresses OC progression via ROS-mediated dual mechanisms: apoptosis induction and mitophagy activation. Our results underscore the translational potential of CA as a promising therapeutic candidate and provide a robust experimental foundation for its further development against OC.