MG132, a proteasome inhibitor decreased the growth of Calu-6 lung cancer cells via apoptosis and GSH depletion.
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.
Han
Yong Hwan
YH
Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu 561-180, Republic of Korea.
Park
Woo Hyun
WH
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007976:Leupeptins / Q000633:toxicity*; D008175:Lung Neoplasms / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D007976:Leupeptins; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D005978:Glutathione; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde