STAT1, STAT3 and p38MAPK are involved in the apoptotic effect induced by a chimeric cyclic interferon-alpha2b peptide

BLANK VC; PEÑA C; ROGUIN, L. P

EXPERIMENTAL CELL RESEARCH

Elsevier

Lugar: Amsterdam. The Netherlands ; Año: 2010 vol. 316 p. 603 - 614

0014-4827

In the search of mimetic peptides of the interferon-α2b molecule (IFN-α2b), we have previouslydesigned and synthesized a chimeric cyclic peptide of the IFN-α2b that inhibits WISH cellproliferation by inducing an apoptotic response. Here, we first studied the ability of this peptide to activate intracellular signaling pathways and then evaluated the participation of some signals inthe induction of apoptosis. Stimulation of WISH cells with the cyclic peptide showed tyrosinephosphorylation of Jak1 and Tyk2 kinases, tyrosine and serine phosphorylation of STAT1 andSTAT3 transcription factors and activation of p38 MAPK pathway, although phosphorylation levels or kinetics were in some conditions different to those obtained under IFN-α2b stimulus. JNK and p44/42 pathways were not activated by the peptide in WISH cells.We also showed that STAT1 and STAT3 downregulation by RNA interference decreased the antiproliferative activity and the amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.