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.

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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