Auranofin induces apoptosis and necrosis in HeLa cells via oxidative stress and glutathione depletion.

Abstract

Auranofin (Au), an inhibitor of thioredoxin reductase, is a known anti‑cancer drug. In the present study, the anti‑growth effect of Au on HeLa cervical cancer cells was examined in association with levels of reactive oxygen species (ROS) and glutathione (GSH). Au inhibited the growth of HeLa cells with an IC50 of ~2 µM at 24 h. This agent induced apoptosis and necrosis, accompanied by the cleavage of poly (ADP‑ribose) polymerase and loss of mitochondrial membrane potential. The pan‑caspase inhibitor, benzyloxycarbonyl‑Val‑Ala‑Asp‑fluoromethylketone, prevented apoptotic cell death and each of the assessed caspase inhibitors inhibited necrotic cell death induced by Au. With respect to the levels of ROS and GSH, Au increased intracellular O2•- in the HeLa cells and induced GSH depletion. The pan‑caspase inhibitor reduced the levels of O2•- and GSH depletion in Au‑treated HeLa cells. The antioxidant, N‑acetyl cysteine, not only attenuated apoptosis and necrosis in the Au‑treated HeLa cells, but also decreased the levels of O2•- and GSH depletion in the cells. By contrast, L‑buthionine sulfoximine, a GSH synthesis inhibitor, intensified cell death O2•- and GSH depletion in the Au‑treated HeLa cells. In conclusion, Au induced apoptosis and necrosis in HeLa cells via the induction of oxidative stress and the depletion of GSH.

• Authors: Bo Ra You, Hye Rim Shin, Bo Ram Han, Suhn Hee Kim, Woo Hyun Park
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 11 Issue 2 Pg. 1428-34 (Feb 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25370167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Antioxidants
• Caspase Inhibitors
• Oligopeptides
• benzyloxycarbonyl-valyl-alanyl-aspartic acid
• Singlet Oxygen
• Auranofin
• Buthionine Sulfoximine
• Glutathione
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Antineoplastic Agents (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Auranofin (pharmacology)
• Buthionine Sulfoximine (pharmacology)
• Caspase Inhibitors (pharmacology)
• Cell Proliferation (drug effects)
• Glutathione (analysis, deficiency, metabolism)
• HeLa Cells
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Necrosis
• Oligopeptides (pharmacology)
• Oxidative Stress (drug effects)
• Singlet Oxygen (analysis, metabolism)