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Relationship between intracellular glutathione level and the mode of cell death induced by pingyangmycin

Kuo-Wei Tai1, Chong-Kuei Lii, Ming-Yung Chou

  • 1Department of Oral and Maxillofacial Surgery, Chung Shan Medical and Dental College Hospital, Taichung, Taiwan.

Oral Oncology
|November 30, 2002
PubMed

Insights

Lowering intracellular glutathione (GSH) levels increases pingyangmycin toxicity in cancer cells, shifting cell death from necrosis to apoptosis. Conversely, increasing GSH levels protects cells from pingyangmycin-induced death.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Intracellular glutathione (GSH) plays a crucial role in cellular defense mechanisms.
  • Understanding the role of GSH in drug toxicity is vital for cancer therapy.
  • Pingyangmycin is an anticancer agent whose efficacy may be modulated by cellular redox status.

Purpose of the Study:

  • To investigate the impact of varying intracellular glutathione (GSH) concentrations on the toxicity of pingyangmycin.
  • To determine how GSH levels influence the mode of cell death induced by pingyangmycin in human squamous cell carcinoma.
  • To explore potential strategies for enhancing pingyangmycin efficacy through GSH modulation.

Main Methods:

  • Artificially altering intracellular GSH levels using D,L-buthionine-S,R-sulfoximine (GSH synthesis inhibitor) and 2-oxothiazolidine-4-carboxylate (OTZ, cysteine precursor).
  • Treating cultured human squamous cell carcinoma cells with pingyangmycin at different GSH concentrations.
  • Analyzing the mode of cell death (necrosis vs. apoptosis) using morphological and biochemical criteria.

Main Results:

  • Decreased intracellular GSH levels significantly enhanced pingyangmycin's toxicity towards tumor cells.
  • Lowering GSH levels induced a switch in cell death from necrosis to apoptosis.
  • Elevated GSH levels, achieved with OTZ treatment, inhibited pingyangmycin-induced cell death, favoring necrosis over apoptosis.

Conclusions:

  • Intracellular glutathione (GSH) concentration critically affects pingyangmycin's toxicity in human squamous cell carcinoma.
  • GSH levels play a key role in determining the mode of cell death induced by pingyangmycin.
  • Modulating cellular GSH levels presents a potential strategy to optimize pingyangmycin-based cancer therapies.

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