title: Antiproliferative and antimetastatic action of quercetin on A549 non-small cell lung cancer cells through its effect on the cytoskeleton.
abstract: To our knowledge, this study is the first to investigate the effect of the dietary flavonoid quercetin on the main cytoskeletal elements, namely microfilaments, microtubules and vimentin intermediate filaments, as well as cytoskeleton-driven processes in A549 non-small cell lung cancer cells. The methyl-thiazol-diphenyl-tetrazolium assay, annexin V/propidium iodide test, electron microscopic examination, cell cycle analysis based on DNA content, real-time PCR assays, in vitro scratch wound-healing assay, fluorescence staining of F-actin, β-tubulin and vimentin were performed to assess the effects of quercetin on A549 cells. Our results showed that quercetin triggered BCL2/BAX-mediated apoptosis, as well as necrosis and mitotic catastrophe, and inhibited the migratory potential of A549 cells. The disassembling effect of quercetin on microfilaments, microtubules and vimentin filaments along with its inhibitory impact on vimentin and N-cadherin expression might account for the decreased migration of A549 cells in response to quercetin treatment. We also suggest that the possible mechanism underlying quercetin-induced mitotic catastrophe involves the perturbation of mitotic microtubules leading to monopolar spindle formation, and, consequently, to the failure of cytokinesis. We further propose that cytokinesis failure could also be a result of the depletion of actin filaments by quercetin. These findings are important to our further understanding of the detailed mechanism of the antitumor activity of quercetin and render this flavonoid a potentially useful candidate for combination therapy with conventional antimicrotubule drugs, nucleic acid-directed agents or novel cytoskeletal-directed agents.
authors.affiliation: Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Poland. Electronic address: ania.klimaszewska@op.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Klimaszewska-Wiśniewska
authors.affiliation: Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Poland. Electronic address: marciah88@wp.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Hałas-Wiśniewska
authors.affiliation: Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Izdebska
authors.affiliation: Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Poland. Electronic address: mgagat@cm.umk.pl.
authors.forename: Maciej
authors.initials: M
authors.lastname: Gagat
authors.affiliation: Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Poland. Electronic address: agrzanka@cm.umk.pl.
authors.forename: Alina
authors.initials: A
authors.lastname: Grzanka
authors.affiliation: Department and Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Poland. Electronic address: d_gr@wp.pl.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Grzanka
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003598:Cytoskeletal Proteins; D050257:Tubulin Modulators; D011794:Quercetin
keywords: Apoptosis; Cytoskeleton; Mitotic catastrophe; Non-small cell lung cancer; Quercetin