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Published on: January 23, 2026

Role of c-Jun in cellular sensitivity to the microtubule inhibitor vinblastine

Toria B Obey1, Christopher S Lyle, Timothy C Chambers

  • 1Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA.

Biochemical and Biophysical Research Communications
|August 23, 2005
PubMed

Insights

The transcription factor c-Jun influences cell death sensitivity to vinblastine, a microtubule inhibitor. Its presence or absence alters how cells respond to this chemotherapy agent, impacting DNA replication during apoptosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Vinblastine is a microtubule inhibitor used in chemotherapy.
  • The transcription factor c-Jun is involved in cellular stress responses and apoptosis.
  • Understanding the precise mechanisms of vinblastine-induced apoptosis is crucial for optimizing cancer therapy.

Purpose of the Study:

  • To investigate the role of c-Jun in the apoptotic response of fibroblasts to vinblastine.
  • To elucidate how c-Jun expression levels affect cellular sensitivity and death pathways.
  • To examine the relationship between c-Jun, vinblastine treatment, and DNA replication during apoptosis.

Main Methods:

  • Fibroblast cell lines with absent (null) or overexpressed c-Jun were utilized.
  • Cells were treated with varying concentrations of vinblastine.
  • Propidium iodide staining and flow cytometry were employed to assess cell fate and DNA content.
  • Mitotic arrest and DNA re-replication were analyzed.

Main Results:

  • c-Jun null cells showed increased sensitivity to low vinblastine concentrations but similar responses at higher concentrations compared to wild-type cells.
  • c-Jun overexpressing cells exhibited significant resistance to vinblastine (12-fold increase in IC50).
  • Vinblastine treatment induced mitotic arrest in all cell types prior to apoptosis.
  • DNA re-replication was prominent in wild-type cells, reduced in c-Jun null cells, and absent in c-Jun overexpressing cells during apoptosis.

Conclusions:

  • c-Jun plays a significant role in determining cellular sensitivity to the microtubule inhibitor vinblastine.
  • c-Jun appears to regulate the pathway to cell death following mitotic arrest induced by vinblastine.
  • Modulating c-Jun expression could be a potential strategy to enhance vinblastine efficacy in cancer treatment.

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