engleski

Sodium salicylate inhibits urokinase activity in MDA MB-231 breast cancer cells

Sodium salicylate (NaS) is a derivate of acetylsalicylic acid or aspirin, used as a nonsteroidal anti-inflammatory drug (NSAID) for centuries, for its analgesic and anti- inflammatory effects. Mechanisms of its action in the cell are still unexplored. It was found to modulate different MAP kinases, as well as NF-κB pathway, but many of these processes were cell- specific. In this study we explored the effect of NaS on cell growth and urokinase activity in MDA MB-231 breast cancer cells. NaS effect on cell viability was assessed by crystal violet staining and propidium iodide exclusion assay. Urokinase activity was assayed by radial caseinolysis and expression of urokinase system components was analyzed on RNA and protein levels by qRT-PCR and Western blot. Sublethal concentrations of NaS decreased cell growth and inhibited proteolysis caused by activated urokinase. Cells were morphologically changed. Inhibition of urokinase activity was a consequence of decrease in urokinase expression and increase in expression of its inhibitors. Analysis of signaling molecules revealed NaS-dependent modulation of ERK and GSK-3β pathway and changes in integrin expression. We propose that NaS causes cellular reprogramming and changes in expression in a set of genes involved in extracellular proteolysis.

Epithelial-mesenchymal transition ; Integrins ; Nonsteroidal anti-inflammatory drug ; TGF-β ; Urokinase plasminogen activator

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