Journal
HUMAN & EXPERIMENTAL TOXICOLOGY
Volume 29, Issue 7, Pages 607-614Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0960327109358733
Keywords
MG132; cell cycle; apoptosis; A549 lung cancer; ROS; GSH
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Funding
- Ministry for Health, Welfare & Family Affairs and Republic of Korea [A084194]
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Carbobenzoxy-Leu-Leu-leucinal (MG132) as a proteasome inhibitor has been shown to induce apoptotic cell death through formation of reactive oxygen species (ROS). In the present study, we evaluated the effects of MG132 on the growth of A549 lung cancer cells in relation to cell growth, ROS and glutathione (GSH) levels. Treatment with MG132 inhibited the growth of A549 cells with an IC(50) of approximately 20 mu M at 24 hours. DNA flow cytometric analysis indicated that 0.5 similar to 30 mu M MG132 induced a GI phase arrest of the cell cycle in A549 cells. Treatment with 10 or 30 mu M MG132 also induced apoptosis, as evidenced by sub-GI cells and annexin V staining cells. This was accompanied by the loss of mitochondrial membrane potential (MMP; Delta Psi m). The intracellular ROS levels including O(2)(center dot-) were strongly increased in 10 or 30 mu M MG132-treated A549 cells but were down-regulated in 0.1, 0.5 or 1 mu M MG132-treated cells. Furthermore, 10 or 30 mu M MG132 increased mitochondrial O2(center dot-) level but 0.1, 0.5 or 1 mu M MG132 decreased that. In addition, 10 or 30 mu M MG132 induced GSH depletion in A549 cells. In conclusion, MG132 inhibited the growth of human A549 cells via inducing the cell cycle arrest as well as triggering apoptosis, which was in part correlated with the changes of ROS and GSH levels. Our present data provide important information on the anti-growth mechanisms of MG132 in A549 lung cancer cells in relation to ROS and GSH.
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