MG132, a proteasome inhibitor decreased the growth of Calu-6 lung cancer cells via apoptosis and GSH depletion.

Abstract

The inhibition of proteasome function has emerged as a useful strategy to maneuver apoptosis. In the present study, we evaluated the effects of MG132 as a proteasome inhibitor on the growth of Calu-6 lung cancer cells in relation to the cell cycle, cell death, reactive oxygen species (ROS) and glutathione (GSH) levels. MG132 dose-dependently inhibited the growth of Calu-6 cells at 24h. DNA flow cytometric analysis indicated that 1-30 microM MG132 induced an S phase arrest in Calu-6 cells. MG132 also induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP; Deltapsi(m)). The pan-caspase inhibitor (Z-VAD) significantly rescued Calu-6 cells from MG132-induced cell death. The intracellular ROS levels including O(2)(-) were increased in MG132-treated Calu-6 cells. MG132 also increased GSH-depleted cell numbers in Calu-6 cells. Z-VAD significantly decreased O(2)(-) levels and GSH-depleted cell numbers in MG132-treated Calu-6 cells. In conclusion, MG132 inhibited the growth of Calu-6 cells via apoptosis and GSH depletion.

• Authors: Yong Hwan Han, Woo Hyun Park
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 24 Issue 4 Pg. 1237-42 (Jun 2010) ISSN: 1879-3177 [Electronic] England
• PMID: 20149858 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Leupeptins
• Proteasome Inhibitors
• Reactive Oxygen Species
• Glutathione
• benzyloxycarbonylleucyl-leucyl-leucine aldehyde

Topics

• Antineoplastic Agents (toxicity)
• Apoptosis
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Glutathione (metabolism)
• Humans
• Leupeptins (toxicity)
• Lung Neoplasms (metabolism)
• Membrane Potentials (drug effects)
• Proteasome Inhibitors
• Reactive Oxygen Species (metabolism)