Protective role of tretinoin and N-acetyl-L-cysteine from antiproliferative action of cigarette smoke extract on alveolar epithelial cells.
To investigate the mechanisms by which tretinoin and N-acetyl-L-cysteine (NAC) reverse the growth inhibition of alveolar epithelial cells induced by cigarette smoke extract (CSE), MTT assay was used to evaluate cell viability. It was observed that both tretinoin and NAC could restore the viability of CSE-inhibited A549 cells. By incubation with fluorescent indicator H2DCFDA, it was documented that CSE-stimulated accumulation of intracellular reactive oxygen species (ROS) was obviously decreased by tretinoin or NAC. Furthermore, using semi-quantitative and real-time quantitative RT-PCR as well as western blot methods, high expression of insulin-like growth factor binding protein-2 (IGFBP-2) in A549 cells treated with CSE was found at both transcriptional and protein levels, and concomitant with the restoration of cell growth after treatment with tretinoin or NAC, down regulation of IGFBP-2 was observed. From the present study, it is concluded that both RA and NAC can antagonize CSE-induced growth arrest of alveolar epithelial cells and that down regulation of IGFBP-2 may play an important role in the process.
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Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, RR China. jiaozongxian9@hotmail.com
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D000111:Acetylcysteine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000737:chemistry*; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D018971:Insulin-Like Growth Factor Binding Protein 2; D017382:Reactive Oxygen Species; D012906:Smoke; D014212:Tretinoin; D000111:Acetylcysteine