The Mechanism of Proteasome Inhibitor-Induced Apoptosis in Lung Cancer Cells.
10.4046/trd.2003.54.4.403
- Author:
Cheol Hyeon KIM
1
;
Kyoung Hee LEE
;
Choon Taek LEE
;
Young Whan KIM
;
Sung Koo HAN
;
Young Soo SHIM
;
Chul Gyu YOO
Author Information
1. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. cgyoo@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Proteasome inhibitor;
Apoptosis;
Lung cancer
- MeSH:
Apoptosis*;
Blotting, Western;
Caspase 3;
Cell Death;
Cell Survival;
Down-Regulation;
Lung Neoplasms*;
Lung*;
Phosphotransferases;
Proteasome Endopeptidase Complex*;
Proteasome Inhibitors;
Bortezomib
- From:Tuberculosis and Respiratory Diseases
2003;54(4):403-414
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Proteasome inhibitors can promote either cell survival or programmed cell death, depending on both the specific type and proliferative status of the cell. However, it is not well known whether inhibition of proteasome activity is related to apoptosis in lung cancer cells. In addition, the exact mechanisms responsible for apoptosis induced by proteasome inhibition are not well understood. In the present study, we have examined the effect of proteasome inhibition on lung cancer cells and tried to test the mechanisms that may be associated with the apoptosis of these cells. METHODS: We examined the effect of proteasome inhibition with MG132 or PS-341 on cell survival in A549 and NCI-H157 lung cancer cells using MTT assay, and analyzed the cleavage of PARP by Western blot analysis to find evidence of apoptosis. Next, we evaluated the activation of caspase 3 by Western blot analysis and the activity of JNK by immunocomplex kinase assay. We also examined the changes in anti-apoptotic pathways like ERK and cIAP1 by Western blot analysis after inhibition of proteasome function. RESULTS: We demonstrated that MG132 reduced cell survival by inducing apoptosis in A549 and NCI-H157 cells. Proteasome inhibition with MG132 or PS-341 was associated with activation of caspase 3 and JNK, reduced expression of activated ERK, and downregulation of cIAP1. CONCLUSION: Apoptosis induced by proteasome inhibition may be associated with the activation of pro-apoptotic pathways like caspase 3 and JNK and the inactivation of anti-apoptotic pathways in lung cancer cells.
