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Published on: February 25, 2016
β-Elemene Triggers Drp1-Dependent Mitochondrial Fission Through CDK1/Cyclin B1 Signaling in Cervical Cancer Cells
Zhifang Li1,2, Ling Tang2, Mingyan Wang3
1Department of Obstetrics and Gynecology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou City, Sichuan Province, China.
Abstract:
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.
Insights
The anti-cancer compound beta-elemene disrupts mitochondrial homeostasis in cervical cancer cells by activating CDK1-dependent Drp1, causing excessive mitochondrial fission and cell death.
Area of Science:
- Cell Biology
- Cancer Research
- Mitochondrial Biology
Background:
- Mitochondrial dynamics (fission/fusion) are crucial for cell survival and metabolism, and are often dysregulated in cancer.
- The sesquiterpene beta-elemene shows anti-tumor potential, but its impact on mitochondrial dynamics in cervical cancer remains unexplored.
Purpose of the Study:
- To investigate if beta-elemene disrupts mitochondrial homeostasis in cervical cancer cells.
- To elucidate the molecular mechanisms underlying beta-elemene's anti-tumor effects on mitochondria.
Main Methods:
- Treatment of HT-3 and Caski cervical cancer cells with beta-elemene.
- Assessment of cell viability, lactate dehydrogenase release, mitochondrial oxidative stress, and respiratory function.
- Analysis of dynamin-related protein 1 (Drp1) phosphorylation and mitochondrial translocation.
- Investigation of cyclin-dependent kinase 1 (CDK1) and cyclin B1 interaction.
- Genetic silencing of CDK1 to evaluate its role in beta-elemene's effects.
Main Results:
- Beta-elemene reduced cervical cancer cell viability and increased cell damage in a dose-dependent manner.
- Treatment induced mitochondrial oxidative stress, impaired respiration, and caused significant mitochondrial fragmentation.
- Beta-elemene promoted Drp1 phosphorylation at Ser616 and its mitochondrial translocation via CDK1 activation.
Conclusions:
- Beta-elemene triggers excessive mitochondrial fission and dysfunction in cervical cancer cells.
- The compound activates a novel pathway involving CDK1-dependent Drp1 activation, leading to anti-tumor effects.
- Targeting mitochondrial dynamics with beta-elemene presents a potential therapeutic strategy for cervical cancer.
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