Caspase inhibitor decreases apoptosis in pyrogallol-treated lung cancer Calu-6 cells via the prevention of GSH depletion.

Abstract

Pyrogallol (PG) is a polyphenol compound and is known to be an O2.- generator. In the present study, we evaluated the anti-apoptotic effects of caspase inhibitors in relation to changes in reactive oxygen species (ROS) and glutathione (GSH) levels in PG-treated human pulmonary adenocarcinoma Calu-6 cells. Treatment with 50 microM PG inhibited the growth of Calu-6 cells approximately 60% and induced apoptosis approximately 17% at 24 h, accompanied by mitochondrial membrane potential loss (DeltaPsim). Treatment with pan-caspase inhibitor (Z-VAD-FMK), caspase-3 inhibitor (Z-DEVD-FMK), caspase-8 inhibitor (Z-IETD-FMK) and caspase-9 inhibitor (Z-LEHD-FMK) significantly prevented apoptosis in PG-treated Calu-6 cells at 24 h. PG increased the ROS and depleted GSH contents in Calu-6 cells. Treatment with each caspase inhibitor did not significantly change the ROS and GSH levels in PG-treated Calu-6 cells at 24 h. However, Z-VAD significantly prevented GSH depletion in PG-treated Calu-6 cells at the late time phase of 72 h. Conclusively, the anti-apoptotic effect of caspase inhibitor on PG-induced Calu-6 cell death was closely related to changes in GSH content rather than ROS levels.

• Authors: Yong Hwan Han, Suhn Hee Kim, Sung Zoo Kim, Woo Hyun Park
• Journal: International journal of oncology (Int J Oncol) Vol. 33 Issue 5 Pg. 1099-105 (Nov 2008) ISSN: 1019-6439 [Print] Greece
• PMID: 18949374 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caspase Inhibitors
• Cysteine Proteinase Inhibitors
• Reactive Oxygen Species
• Pyrogallol
• Caspases
• Glutathione

Topics

• Adenocarcinoma (enzymology, pathology)
• Apoptosis (drug effects)
• Caspase Inhibitors
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cysteine Proteinase Inhibitors (pharmacology)
• Glutathione (metabolism)
• Humans
• Lung Neoplasms (enzymology, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Pyrogallol (pharmacology)
• Reactive Oxygen Species (metabolism)
• Time Factors