title: Long-term nitric oxide exposure enhances lung cancer cell migration.
abstract: Nitric oxide (NO) found in the vicinity of lung cancer cells may play a role in the regulation of cancer cell behaviors. To explore the possible effects of NO on cell motility, human lung cancer cells were exposed to nontoxic concentrations of NO for 0-14 days, and the migratory characteristics of the cells were determined. The present study found that long-term treatment with NO significantly enhanced cell migration in a dose- and time-dependent manner. Furthermore, we found that the increased migratory action was associated with the increased expression of caveolin-1 (Cav-1), which in turn activated the focal adhesion kinase (FAK) and ATP-dependent tyrosine kinase (Akt) pathways. Notably, the NO-treated cells exhibited an increased number of filopodia per cell, as well as an increase in the levels of cell division cycle 42 (Cdc42) protein. Together, these results indicate that extended NO exposure has a novel effect on cell migration through a Cav-1-dependent mechanism, a finding that strengthens our understanding of cancer biology.
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences and Cell-based Drug and Health Product Development Research Unit, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Arpasinee
authors.initials: A
authors.lastname: Sanuphan
authors.forename: Preedakorn
authors.initials: P
authors.lastname: Chunhacha
authors.forename: Varisa
authors.initials: V
authors.lastname: Pongrakhananon
authors.forename: Pithi
authors.initials: P
authors.lastname: Chanvorachote
mesh_terms: D051242:Caveolin 1 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D051242:Caveolin 1; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D051417:Focal Adhesion Kinase 1; D051057:Proto-Oncogene Proteins c-akt