Pyrazine, 2-ethylpyridine, and 3-ethylpyridine are cigarette smoke components that alter the growth of normal and malignant human lung cells, and play a role in multidrug resistance development.

Abstract

Lung cancer is one of the few human diseases for which the primary etiological agent, cigarette smoke (CS), has been described; however, the precise role of individual cigarette smoke toxicant in tumor development and progression remains to be elusive. The purpose of this study was to assess in vitro the effects of previously identified cigarette smoke components, pyrazine, 2-ethylpyridine, and 3-ethylpyridine, on non-tumorigenic (MRC5) and adenocarcinomic (A549) human lung cell lines. Our data showed that the administration of three cigarette smoke components in combination perturbed the proliferation of both normal and adenocarcinomic cells. Study of malignant cells revealed that CS components were cytotoxic at high concentration (10(-6) M) and stimulatory in a dose-dependent manner at lower concentrations (10(-8) M to 10(-10) M). This adverse effect was enhanced when adenocarcinomic cells were maintained in hypoxia resembling intratumoral environment. Furthermore, exposure to pyrazine, 2-ethylpyridine, and 3-ethylpyridine induced oxidative stress in both normal and malignant cells. Finally, assessment of P-gp activity revealed that multidrug resistance was induced in CS component exposed adenocarcinomic lung cells and the induction was augmented in hypoxia. Taken together, pyrazine, 2-ethylpyridine, and 3-ethylpyridine adversely altered both normal and diseased lung cells in vitro and data collected from this study may help lung cancer patients to understand the importance of quitting smoking during lung cancer treatment.

• Authors: Min Liu, Wak-Kim Poo, Yu-Ling Lin
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 98 Issue 1 Pg. 18-26 (Feb 2015) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 25449333 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Pyrazines
• Pyridines
• Smoke
• 2-ethylpyridine
• 3-ethylpyridine

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm
• Humans
• Lung (drug effects)
• Lung Neoplasms (drug therapy, pathology)
• Oxidative Stress (drug effects)
• Pyrazines (toxicity)
• Pyridines (toxicity)
• Smoke
• Tobacco