β‐Elemene Triggers Drp1‐Dependent Mitochondrial Fission Through CDK1/Cyclin B1 Signaling in Cervical Cancer Cells

Mitochondrial dynamics, regulated by fission and fusion, are frequently altered in cancers, influencing cell survival and metabolism. The sesquiterpene β-elemene exhibits anti-tumor activity, but its effect on mitochondrial dynamics in cervical cancer is unknown. This study investigated whether β-elemene exerts its anti-tumor effects by disrupting mitochondrial homeostasis. We found that β-elemene treatment dose-dependently reduced viability and increased lactate dehydrogenase release in HT-3 and Caski cervical cancer cells. In HT-3 cells, β-elemene induced mitochondrial oxidative stress, impaired respiratory function, and triggered extensive mitochondrial fragmentation. Mechanistically, β-elemene promoted phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and its translocation to mitochondria. Furthermore, β-elemene enhanced the interaction between cyclin-dependent kinase 1 (CDK1) and cyclin B1. Genetic silencing of CDK1 abrogated β-elemene-induced Drp1 activation, mitochondrial fragmentation, and bioenergetic deficits. Collectively, these data identify a novel pathway through which β-elemene drives CDK1-dependent Drp1 activation, leading to excessive mitochondrial fission and dysfunction in cervical cancer cells.