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)
|