期刊
NATURAL PRODUCT RESEARCH
卷 30, 期 11, 页码 1327-1331出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14786419.2015.1055265
关键词
Convallatoxin; digitoxigenin monodigitoxoside; proliferation; migration; invasion; A549 cell line; lung cancer
资金
- Brazilian agency CNPq/MCTI [472544/2013-6, 490057/2011-0]
- Marie Curie Foundation IRSES
- European Community Marie Curie Foundation by IRSES [2011-IRSES-295251]
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.
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