engleski

Antitumour activity of luteolin in human colon cancer SW620 cells is mediated by the ERK/FOXO3a signalling pathway

The aim of this study was to investigate the mechanism of the anticancer activity of luteolin, a member of the flavonoid family, in metastatic human colon cancer SW620 cells. Studies have shown that luteolin possesses many beneficial effects in vitro and in vivo, including antioxidant, anti- inflammatory, antibacterial, antidiabetic and antiproliferative. Luteolin dose-dependently (1, 2, 5, 10 μmol/L) reduced the viability (XTT Cell Viability Kit) and proliferation of SW620 cells and increased the expression of antioxidant enzymes. Expression of proteins was determined by western blot. The expression of antiapoptotic protein Bcl-2 decreased, whereas the expression of proapoptotic proteins Bax and caspase-3 increased by luteolin treatment, resulting in increased poly (ADP-ribose) polymerase (PARP) cleavage and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) positivity. Luteolin also increased the expression of autophagic proteins Beclin-1, autophagy-related protein 5 (Atg5) and microtubule-associated protein 1A/1B-light chain 3 beta-I/II (LC3B-I/II), while the usage of 3- methyladenine suggested a prosurvival role of autophagy. Moreover, treatment with luteolin induced reversal of the epithelial- mesenchymal transition process through the suppression of the wingless related integration site protein (Wnt)/β- catenin pathway. The cytotoxic activity of luteolin coincided with the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and forkhead box O3a (FOXO3a). Treatment with the mitogenactivated protein kinase (MEK) inhibitor PD0325901 inhibited ERK-dependent FOXO3a phosphorylation, resulting in increased FOXO3a expression and apoptosis, with the suppression of autophagy. The results of the current study suggest the antitumour activity of luteolin in SW620 cells through the ERK/FOXO3a-dependent mechanism, as well as its antimetastatic potential.

anticancer activity ; apoptosis ; autophagy ; flavonoid ; forkhead box O3a

nije evidentirano