title: Inhibition of cell proliferation, invasion and migration by the cardenolides digitoxigenin monodigitoxoside and convallatoxin in human lung cancer cell line.
abstract: Cardiac glycosides consist of a large family of naturally derived compounds that are clinically used to treat congestive heart failure, and also present anticancer properties. In this study, the cytotoxic effects of two cardenolides, digitoxigenin monodigitoxoside (DGX) and convallatoxin (CON) were screened in four human tumour cell lines. Both compounds showed anti-proliferative effects in all tumour cells, at nanomolar concentrations. Since the human lung cancer cell line A549 was the most sensitive, we investigated the anti-proliferative, anti-migratory and anti-invasive effects of these cardenolides. DGX and CON reduced A549 cell migration, being able to reduce more than 90% of cell invasion. Their effects on the expression of key regulators of metastatic mechanism showed decreased levels of MMP-2, MMP-9 and p-FAK. Both compounds also presented low toxicity for healthy cells. Finally, this work provides the first insights into the effects of these cardenolides on key steps of lung cancer metastasis.
authors.affiliation: a Departamento de Ciências Farmacêuticas , Centro de Ciências da Saúde, Universidade Federal de Santa Catarina , Florianópolis , SC , Brazil.
authors.forename: Naira F Z
authors.initials: NF
authors.lastname: Schneider
authors.affiliation: a Departamento de Ciências Farmacêuticas , Centro de Ciências da Saúde, Universidade Federal de Santa Catarina , Florianópolis , SC , Brazil.
authors.forename: Fabiana C
authors.initials: FC
authors.lastname: Geller
authors.affiliation: a Departamento de Ciências Farmacêuticas , Centro de Ciências da Saúde, Universidade Federal de Santa Catarina , Florianópolis , SC , Brazil.
authors.forename: Lara
authors.initials: L
authors.lastname: Persich
authors.affiliation: a Departamento de Ciências Farmacêuticas , Centro de Ciências da Saúde, Universidade Federal de Santa Catarina , Florianópolis , SC , Brazil.
authors.forename: Lucas L
authors.initials: LL
authors.lastname: Marostica
authors.affiliation: b Faculdade de Farmácia, Departamento de Produtos Farmacêuticos , Universidade Federal de Minas Gerais , Belo Horizonte , MG , Brazil.
authors.forename: Rodrigo M
authors.initials: RM
authors.lastname: Pádua
authors.affiliation: c Department of Biology , Friedrich-Alexander Universität , Erlangen-Nürnberg , Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kreis
authors.affiliation: b Faculdade de Farmácia, Departamento de Produtos Farmacêuticos , Universidade Federal de Minas Gerais , Belo Horizonte , MG , Brazil.
authors.forename: Fernão C
authors.initials: FC
authors.lastname: Braga
authors.affiliation: a Departamento de Ciências Farmacêuticas , Centro de Ciências da Saúde, Universidade Federal de Santa Catarina , Florianópolis , SC , Brazil.
authors.forename: Cláudia M O
authors.initials: CM
authors.lastname: Simões
mesh_terms: D000072283:A549 Cells; D002298:Cardenolides / Q000494:pharmacology*; D002301:Cardiac Glycosides / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004073:Digitoxigenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000188:drug therapy; D013328:Strophanthins / Q000494:pharmacology
chemical_list: D002298:Cardenolides; D002301:Cardiac Glycosides; D013328:Strophanthins; D004073:Digitoxigenin; C035486:digitoxigenin monodigitoxoside; C000505:convallatoxin
keywords: A549 cell line; Convallatoxin; digitoxigenin monodigitoxoside; invasion; lung cancer; migration; proliferation