engleski

The effect of sodium salicylate on the biology of MDA MB-231 breast cancer cells

Sodium salicylate (NaS) is a derivative of natural compound acetylsalicylic acid (aspirin) which is commonly used as a non-steroidal anti-inflammatory drug (NSAID). NaS lacks aspirin’s inhibitory effect on prostaglandins, but still has anti-inflammatory functions and shares with aspirin certain downstream interactions. At present, mechanisms of NaS action are still not fully explained. In vitro it was shown that NaS targets intracellular signaling mechanisms such as mitogen activated MAP kinases cascade and influences several transcription factors such as NF-kB and AP-1. Recently it was found that it can activate AMPK, central cellular metabolic regulator. The aim of our study was to elucidate the effect of NaS on the morphology, proliferation and urokinase plasminogen activation (uPA) system of MDA MB-231 breast cancer cells. Cells treated for 24 h with NaS exhibited morphology changes and cell proliferation was inhibited in concentration range 5 to 20 mM. We also investigated effect of NaS on uPA system. Its main component is uPA, an extracellular protease involved in extracellular matrix remodeling. By plasmin activation it can regulate tissue degradation. These processes regulate normal tissue reconstruction, but also tumor invasiveness and metastasis. In our experiments, NaS decreased extracellular uPA activity of treated cells up to a 90 % of control cells in dose- and time-dependent manner. To examine the nature of uPA activity decrease, components of the uPA system, such as uPA, its inhibitors PAI-1 and PAI-2 and receptor uPAR were analyzed. We observed change in uPA/PAI-1 ratio in treated cells on RNA and protein level. Furthermore, we investigated the influence of NaS on signaling pathways involving NF-kB, β catenin and MAP kinases. Morphology changes lead us to analyze integrin expression. We found selective decrease in αv and β5 expression. Our results suggest that NaS could be an interesting modulator of uPA activity in certain types of cancer cells.

sodium salicylate ; urokinase plasminogen activator

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