title: Cigarette smoke effects on TSPO and VDAC expression in a cellular lung cancer model.
abstract: As redox iron and copper ions are found in lung pleural fluid and parenchyma, we aimed to examine the effect of cigarette smoke (CS) alone and the combined effects of CS and redox metals, iron and copper ions, containing medium (saliva), on epithelial H1299 lung cancer cells. We also examined the expression levels of the anticarcinogenic and proapoptotic 18 kDa translocator protein (TSPO) and its closely associated protein voltage-dependent anion channel (VDAC). H1299 cells were subjected to western blot analysis using anti-TSPO and anti-VDAC antibodies. With the former, the 18 kDa band appeared as expected and a 72 kDa band also appeared. It may be assumed that in H1299 lung cancer cells, an additional form of TSPO protein appears as a four-unit tetrameric complex, which is affected by CS exposure. A significant decrease in the expression level of the 72 kDa protein occurred following only 60 min of CS exposure, whereas VDAC protein levels were increased following only 30 min of CS exposure. These results, together with our previous related studies, suggest a comprehensive two-arm novel paradigm for lung cancer induced by CS, and mediated by an altered TSPO protein, possibly resulting from both the 72 kDa TSPO degradation and redox metal ion-induced enhancement of free radical attack. We suggest that both of the most important proapoptotic and anticancer proteins, p53 and TSPO, are damaged by CS, paving the way for lung cancer initiation and progression.
authors.affiliation: Department of Neuroscience, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Gavish
authors.forename: Shiri
authors.initials: S
authors.lastname: Cohen
authors.forename: Rafael
authors.initials: R
authors.lastname: Nagler
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D018079:Receptors, GABA / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*; D014407:Tumor Cells, Cultured; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism*
chemical_list: D018079:Receptors, GABA; C499229:TSPO protein, human; C494762:VDAC1 protein, human; D050995:Voltage-Dependent Anion Channel 1