Naslov
Sodium Salicylate Inhibits Urokinase Activity in MDA MB-231 Breast Cancer Cells

Autori
Madunić, Josip ; Horvat, Luka ; Majstorović, Ivana ; Jodłowska, Iga ; Antica, Mariastefania ; Matulić, Maja

Izvornik
Clinical breast cancer (1526-8209) 17 (2017), 8; 629-637

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

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

Sažetak
Introduction Sodium salicylate (NaS) is a derivate of acetylsalicylic acid or aspirin, used as a nonsteroidal anti-inflammatory drug for centuries, for its analgesic and anti- inflammatory effects. It was found to modulate different signaling pathways, in a cell- specific way. Here, we explore the effect of NaS on cell growth and urokinase activity in MDA MB-231 breast cancer cells. Materials and Methods We analyzed the effect of NaS treatment on cell growth by flow cytometry and viability test. The transwell migration assay was used to study the migratory response of the cells. The gene expression was analyzed by qRT-PCR on RNA level and by Western blot analysis on protein level. Urokinase activity was assessed by caseinolysis. Results Sublethal concentrations of NaS decreased cell growth and inhibited urokinase activity. The latter was a consequence of decrease in urokinase expression and increase in expression of its inhibitors. Analysis of signaling molecules revealed activation of transforming growth factor-β signaling, increase in master transcription factors for epithelial-mesenchymal transition and changes in integrin expression. Conclusions We propose that NaS causes partial cellular reprogramming through transforming growth factor-β signaling which, together with direct NaS influence, causes changes in expression in a set of genes involved in extracellular proteolysis. These data could be beneficial for the development of new therapeutic approaches in invasive breast cancer treatment.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA