Cigarette smoke extract (CSE) contains abundant oxidants and free radicals. Oxidative stress caused by cigarette smoking results in the destruction of the alveolar cell walls and emphysema. However, there exists discrepancy about how CSE works in the process. In the present study, we observed the effect of CSE on the cell growth of type II alveolar epithelial cell-derived A549 cell line, and provided molecular understanding of this effect. The MTT assay results showed that CSE decreased the cell viability of A549 cells in a dose- and time-dependent manner, and cell cycle was arrested in G(1)/S phase. Furthermore, CSE-induced apoptosis of A549 cells was verified by Hoechst 33258 staining, electron microscopy in morphology, and the appearance of DNA fragmentation and annexin V-FITC/propidium iodide (PI) staining assay at molecular level. It was found that CSE treatment resulted in the upregulation of Fas/APO-1 receptor and activation of caspase-3. CSE also initiated accumulation of intracellular reactive oxygen species, which was detected by laser confocal microscopy. Taken together, CSE could inhibit the cell growth and induce apoptosis of A549 cells through Fas receptor pathway. Oxidative stress caused by CSE may be the radical factor leading to apoptosis as well as cell growth inhibition in alveolar epithelial cells.
Apoptosis ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Epithelial Cells ; drug effects ; Humans ; Lung Neoplasms ; pathology ; Pulmonary Alveoli ; cytology ; drug effects ; pathology ; Smoke ; adverse effects ; Tobacco ; toxicity

Wnt5a is a representative Wnt ligand that regulates multiple cellular functions through the Wnt5a non-classical pathway. Although Wnt5a has been implicated in various pathological conditions, its role in cancer is ambiguous and might involve methyl modifications, distinct mRNA isoforms, as well as different downstream pathways. Therefore, it is an essential factor in cancers' progression (invasion, migration, proliferation, and epithelial-mesenchymal transition), and a potential biomarker for prognosis and treatment.