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Gossypol induces apoptosis in ovarian cancer cells through oxidative stress

Jia Wang1, Lixu Jin, Xiaoyu Li

  • 1The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.

Molecular Biosystems
|March 28, 2013
PubMed

Insights

Gossypol induces ovarian cancer cell death via oxidative stress, altering cellular glutathione (GSH) levels and redox states of key proteins. This study reveals gossypol

Area of Science:

  • Biochemistry
  • Cell Biology
  • Proteomics

Background:

  • Ovarian cancer remains a significant health challenge.
  • Gossypol is a potential anti-cancer agent.
  • Oxidative stress plays a role in cancer cell death.

Purpose of the Study:

  • To investigate the effects of gossypol on ovarian cancer cells at the metabolomic and redox proteomic levels.
  • To identify specific proteins and metabolic pathways affected by gossypol treatment.
  • To elucidate the mechanism of gossypol-induced apoptosis in ovarian cancer.

Main Methods:

  • Metabolomic analysis of untreated and gossypol-treated SKOV3 ovarian cancer cells.
  • Redox proteomics using double labeling and LC-MS-MS to identify changes in cysteine thiol-redox states.
  • Analysis of metabolite levels, including glutathione (GSH), aspartic acid, and FAD.
  • Characterization of redox-sensitive cysteine residues in key proteins like PKM2, HSP60, and malate dehydrogenase.

Main Results:

  • Gossypol treatment induced cell death in SKOV3 cells through oxidative stress.
  • Gossypol decreased cellular levels of GSH, aspartic acid, and FAD.
  • Redox proteomic analysis identified altered thiol-redox states in 545 cysteine-containing peptides from 356 proteins.
  • Specific cysteine residues in HSP60 showed differential responses to gossypol, influenced by GSH levels and oxidation/sulfation.
  • Redox-sensitive proteins identified are involved in metabolism and stress responses.

Conclusions:

  • Gossypol induces apoptosis in ovarian cancer cells via oxidative stress.
  • Cellular GSH levels are critical in regulating thiol/disulfide ratios and protein redox states.
  • The study provides insights into gossypol's mechanism of action and identifies potential therapeutic targets.

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