The attenuation of MG132, a proteasome inhibitor, induced A549 lung cancer cell death by p38 inhibitor in ROS-independent manner.
MG132, as a proteasome inhibitor, can induce apoptotic cell death through formation of reactive oxygen species (ROS). In this study, we investigated the effects of MAPK (MEK, JNK, and p38) inhibitors on MG132-treated A549 lung cancer cells in relation to cell growth, cell death, ROS, and glutathione (GSH) levels. Treatment with 10 microM MG132 inhibited the growth of A549 cells at 24 h. MG132 also induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP; deltapsi(m)). ROS were not increased in MG132-treated A549 cells. MG132 increased GSH-depleted cell numbers and decreased GSH levels. MEK and JNK inhibitors did not strongly affect cell growth, cell death, ROS, and GSH levels in MG132-treated A549 cells. In contrast, p38 inhibitor reduced cell growth inhibition, apoptosis, and MMP (deltapsi(m)) loss by MG132. However, p38 inhibitor did not change ROS level and GSH content. In conclusion, MG132 inhibited the growth of A549 cells via apoptosis without formation of ROS. Treatment with p38 inhibitor rescued some cells from MG132-induced apotposis, which was not affected by ROS and GSH level changes.
Han
Yong Hwan
YH
Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu, Republic of Korea.
Moon
Hwa Jin
HJ
You
Bo Ra
BR
Park
Woo Hyun
WH
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007976:Leupeptins; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde