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Cancer cell cycle modulated by a functional coupling between sigma-1 receptors and Cl- channels

Adrien Renaudo1, Sébastien L'Hoste, Hélène Guizouarn

  • 1UNSA CNRS UMR 6548, Laboratoire de Physiologie Cellulaire & Moléculaire des Systèmes Intégrés, Université de Nice Sophia-Antipolis, 06108 Nice Cedex 2, France.

The Journal of Biological Chemistry
|November 24, 2006
PubMed

Insights

Selective sigma ligands inhibit volume-regulated chloride channels (VRCC) in cancer cells, impacting cell cycle and apoptosis. Sigma-1 receptors regulate cell volume and protect against programmed cell death.

Area of Science:

  • Cell Biology
  • Molecular Pharmacology
  • Oncology

Background:

  • The sigma-1 receptor is an intracellular protein and a known tumor biomarker.
  • Its precise function in cellular processes, particularly in cancer, remains largely unelucidated.

Purpose of the Study:

  • To investigate the role of sigma-1 receptors in regulating cell volume and their potential as therapeutic targets in cancer.
  • To determine the effect of sigma ligands on volume-regulated chloride channels (VRCC) and cancer cell proliferation.

Main Methods:

  • Utilized highly selective sigma ligands and VRCC blockers in small cell lung cancer, T-leukemia, and HEK cells.
  • Performed cell cycle analysis, proliferation rate assays, and volume measurements under hypotonic conditions.
  • Investigated apoptosis resistance using staurosporine treatment.

Main Results:

  • Selective sigma ligands inhibit VRCC in cancer cells, leading to cell cycle arrest and p27 accumulation.
  • Sigma-1 receptor-transfected cells exhibit reduced proliferation and delayed VRCC activation.
  • Sigma-1 receptors modulate regulatory volume decrease and confer resistance to apoptosis.

Conclusions:

  • Sigma-1 receptors play a critical role in cell volume regulation and influence cell destiny.
  • Targeting sigma-1 receptors via VRCC modulation presents a novel strategy for cancer therapy.

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