title: 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.affiliation: Department of Life Science, Chinese Culture University, Taipei, Taiwan, Republic of China; Graduate Institute of Biotechnology, Chinese Culture University, Taipei, Taiwan, Republic of China. Electronic address: lm@faculty.pccu.edu.tw.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Life Science, Chinese Culture University, Taipei, Taiwan, Republic of China.
authors.forename: Wak-Kim
authors.initials: WK
authors.lastname: Poo
authors.affiliation: Graduate Institute of Biotechnology, Chinese Culture University, Taipei, Taiwan, Republic of China.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Lin
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D011719:Pyrazines / Q000633:toxicity*; D011725:Pyridines / Q000633:toxicity*; D012906:Smoke; D014026:Nicotiana
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011719:Pyrazines; D011725:Pyridines; D012906:Smoke; C051672:2-ethylpyridine; C039675:3-ethylpyridine
keywords: 2-Ethylpyridine; 3-Ethylpyridine; Cigarette smoke; Drug resistance; Oxidative stress; Pyrazine