Ketoprofen suppresses triple negative breast cancer cell growth by inducing apoptosis and inhibiting autophagy

Indrajit Patra, Rana Hussein Naser, Fadhil Hussam, Noora M. Hameed, Mustafa M. Kadhim, Irshad Ahmad, Sura A. Awadh, Doaa A. Hamad, Rosario Mireya Romero Parra, Yasser Fakri Mustafa

Resultado de la investigación: Artículo CientíficoArtículo originalrevisión exhaustiva

Resumen

Background: Triple-negative breast cancer (TNBC) is an invasive phenotype with undesirable clinical features, poor prognosis, and therapy resistance. Ketoprofen is a Non-steroidal anti-inflammatory drug (NSAID) with anti-tumor properties. Aim: To investigate the effects of Ketoprofen on apoptosis and autophagy in TNBC cell line MDA-MB-231. Methods: The cytotoxic activity of Ketoprofen was assayed by the MTS method. Flowcytometry was utilized to measure the number of apoptotic MDA-MB-231 cells. The expression levels of apoptosis and autophagy markers, JAK2 and STAT3 were determined using quantitative real time-PCR (qRT-PCR) and western blotting methods. Results: Ketoprofen significantly decreased the proliferation of MDA-MB-231 cells compared to control cells. It also considerably induced apoptosis and apoptotic markers in these cells in comparison to controls. Treating the MADA-MB-231 cell line with Ketoprofen had an inhibitory effect on autophagy markers in this cell line. The use of FasL, as a death ligand, and ZB4, as an antibody that blocks the extrinsic pathway of apoptosis, revealed the involvement of the extrinsic pathway in the apoptosis-stimulating effect of Ketoprofen in the MADA-MB-231 cell line. Ketoprofen also hindered the phosphorylation and activation of JAK2 and STAT molecules leading to the inhibition of the JAK/STAT pathway in this TNBC cell line. Conclusion: The outcomes of this study uncovered the anti-TNBC activity of Ketoprofen by inducing apoptosis and inhibiting viability and autophagy in MADA-MB-231 cells. Our data also suggested that Ketoprofen impedes apoptosis in TNBC cells by two different mechanisms including the induction of the extrinsic apoptotic pathway and inhibition of the JAK/STAT signaling.

Idioma originalInglés estadounidense
Páginas (desde-hasta)85-95
-11
PublicaciónMolecular Biology Reports
Volumen50
N.º1
DOI
EstadoIndizado - ene. 2023

Nota bibliográfica

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature B.V.

Huella

Profundice en los temas de investigación de 'Ketoprofen suppresses triple negative breast cancer cell growth by inducing apoptosis and inhibiting autophagy'. En conjunto forman una huella única.

Citar esto