The anti-apoptotic effects of caspase inhibitors on propyl gallate-treated HeLa cells in relation to reactive oxygen species and glutathione levels.

Abstract

Propyl gallate (PG) as a synthetic antioxidant is widely used in processed food, cosmetics and medicinal preparations. Despite the assumed low toxicity of PG, it exerts a variety of effects on tissue and cell functions. In the present study, we evaluated the anti-apoptotic effects of caspase inhibitors on PG-treated human cervix adenocarcinoma HeLa cells in relation to the changes of reactive oxygen species (ROS) and glutathione (GSH) levels. PG induced apoptosis in a dose-dependent manner, as evidenced by sub-G1 cells and annexin V staining cells. Treatment with pan-caspase inhibitor, caspase-3 inhibitor, caspase-8 inhibitor or caspase-9 inhibitor significantly prevented apoptosis in PG-treated HeLa cells at 24 h. The intracellular ROS levels including O (2) (*-) were increased or decreased in PG-treated HeLa cells depending on the incubation times (1 or 24 h). PG depleted intracellular GSH content in HeLa cells at 24 h. Treatment with caspase inhibitor reduced ROS levels and significantly prevented GSH depletion in PG-treated HeLa cells at 24 h. In conclusion, PG induced apoptosis in HeLa cells. The anti-apoptotic effect of caspase inhibitor on PG-induced HeLa cell death was closely related to the reduction of ROS levels, especially mitochondrial O (2) (*-) , as well as to the inhibition of GSH depletion.

• Authors: Yong Hwan Han, Hwa Jin Moon, Bo Ra You, Woo Hyun Park
• Journal: Archives of toxicology (Arch Toxicol) Vol. 83 Issue 9 Pg. 825-33 (Sep 2009) ISSN: 1432-0738 [Electronic] Germany
• PMID: 19434396 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Chloromethyl Ketones
• Annexin A5
• Antioxidants
• Caspase Inhibitors
• Enzyme Inhibitors
• Oligopeptides
• Reactive Oxygen Species
• benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
• benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone
• benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
• Propyl Gallate
• Caspase 3
• Caspase 8
• Caspase 9
• Glutathione

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Annexin A5 (metabolism)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Caspase 9 (metabolism)
• Caspase Inhibitors
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (pharmacology)
• G1 Phase (drug effects)
• Glutathione (metabolism)
• HeLa Cells
• Humans
• Oligopeptides (pharmacology)
• Propyl Gallate (pharmacology)
• Reactive Oxygen Species (metabolism)
• Time Factors