Phosphorylation of eIF2α suppresses cisplatin-induced A549 cell apoptosis via p38 inhibition.

Abstract

Cisplatin-based chemotherapy is considered a golden standard for treatment of advanced non-small cell lung cancer (NSCLC). However, drug resistance is one of the major problems in NSCLC chemotherapy. The mechanisms and related biological pathways that contribute to chemoresistance are relatively poorly understood. Here, we demonstrated that the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) suppresses cisplatin-induced A549 cell apoptosis. Cisplatin induced eIF2α phosphorylation through protein kinase RNA. Importantly, phospho-eIF2α inhibited cisplatin-induced A549 cells apoptosis, at least in part, by suppressing the p38 pathway. Moreover, analysis of tissue microarrays information demonstrated that phospho-eIF2α predicted a poor prognosis in patients with NSCLC. Taken together, these results provide a potential mechanism that is used for explaining how eIF2α promotes cisplatin resistance in A549 cells. Therefore, the regulation of eIF2α may improve treatment outcomes of cisplatin-based chemotherapy for patients with NSCLC.

• Authors: Liang Guo, Run Chen, Nan Ma, Haibo Xiao, Yin Chen, Fei Chen, Ju Mei, Fangbao Ding, Hong Zhong
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 28 Issue 4 Pg. 268-73 (May 2013) ISSN: 1557-8852 [Electronic] United States
• PMID: 23570372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cinnamates
• Enzyme Inhibitors
• Eukaryotic Initiation Factor-2
• Imidazoles
• Pyridines
• salubrinal
• eIF-2 Kinase
• p38 Mitogen-Activated Protein Kinases
• Thiourea
• SB 203580
• Cisplatin

Topics

• Aged
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism)
• Cell Line, Tumor
• Cinnamates (pharmacology)
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (pharmacology)
• Eukaryotic Initiation Factor-2 (metabolism)
• Female
• Humans
• Imidazoles (pharmacology)
• Lung Neoplasms (drug therapy, metabolism)
• Male
• Middle Aged
• Phosphorylation (drug effects)
• Prognosis
• Pyridines (pharmacology)
• Signal Transduction
• Thiourea (analogs & derivatives, pharmacology)
• Tissue Array Analysis
• eIF-2 Kinase (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)