Induction of Tca8113 tumor cell apoptosis by icotinib is associated with reactive oxygen species mediated p38-MAPK activation.

Abstract

Icotinib, a selective EGFR tyrosine kinase inhibitor (EGFR-TKI), has been shown to exhibit anti-tumor activity against several tumor cell lines. However, the exact molecular mechanism of icotinib's anti-tumor effect remains unknown. This study aims to examine the zytotoxic effect of icotinib on Tca8113 cells and its potential molecular mechanism. Icotinib significantly resulted in dose-dependent cell death as determined by MTT assay, accompanied by increased levels of Bax and DNA fragmentation. Icotinib could also induce Reactive Oxygen Species (ROS) generation. Further studies confirmed that scavenging of reactive oxygen species by N-acetyl-L-cysteine (NAC), and pharmacological inhibition of MAPK reversed icotinib-induced apoptosis in Tca8113 cells. Our data provide evidence that icotinib induces apoptosis, possibly via ROS-mediated MAPK pathway in Tca8113 cells.

• Authors: Cailing Yang, Jianguo Yan, Guoyan Yuan, Yinghua Zhang, Derong Lu, Mingxin Ren, Weigang Cui
• Journal: Die Pharmazie (Pharmazie) Vol. 69 Issue 8 Pg. 629-32 (Aug 2014) ISSN: 0031-7144 [Print] Germany
• PMID: 25158575 (Publication Type: Journal Article)

Chemical References

• Crown Ethers
• Quinazolines
• Reactive Oxygen Species
• icotinib
• p38 Mitogen-Activated Protein Kinases

Topics

• Apoptosis (drug effects)
• Cell Death (drug effects)
• Cell Line, Tumor
• Crown Ethers (pharmacology)
• Enzyme Activation (drug effects)
• Humans
• Oxidative Stress (drug effects)
• Quinazolines (pharmacology)
• Reactive Oxygen Species (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)