BLANK viviana Claudia
congresos y reuniones científicas
The apoptotic effect induced by a chimeric cyclic interferon-alpha2b peptide is mediated by STAT1, STAT3 and p38MAPK signaling
Congreso; Annual Meeting of the Society of Leukocyte Biology, International Cytokine Society and International Society for Interferon and Cytokine Research; 2009
Institución organizadora:
Society of Leukocyte Biology, International Cytokine Society and International Society for Interferon and Cytokine Research
the apoptotic effect induced by a chimeric cyclic interferon-a2b peptide is mediated by Stat1, stat3 and p38mapk signaling. Viviana C. Blank1, Clara Peña1 and Leonor P. Roguin1. 1Institute of Biochemistry and Biophysics (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina. In the search of mimetic peptides of the interferon-a2b molecule (IFN-a2b), we have previously designed and synthesized a chimeric cyclic peptide mainly containing IFN-a2b sequences 122-137 and 30-35. This peptide inhibits IFN-a2b binding to receptors and exerts an antitumor action on WISH cells 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 these signals in the induction of apoptosis. Stimulation of WISH cells with the cyclic peptide induced tyrosine phosphorylation of different proteins involved in the Jak/STAT pathway. Thus, Jak1 was phosphorylated after 10 min of incubation with the cyclic peptide, whereas Tyk2 activation was observed after 60 min. Phosphorylation of STAT1 and STAT3 was found after 60 and 20 min of peptide treatment, respectively. When MAPK signaling pathways were evaluated, a significant activation of p38 MAPK was obtained in WISH cells treated with the chimeric derivative, although no activation of JNK and p44/42 MAPKs was observed. We also showed that STAT1 and STAT3 downregulation by RNA interference decreased ~50% (p<0.05) the antiproliferative activity induced by the peptide. Furthermore, after incubating STAT1- or STAT3-interfered cells with the cyclic peptide, the amount of hypodiploid cells decreased from 28±4% (control) to 20±2% (p<0.05). Pharmacological inhibition of p38 MAPK diminished near 30% the peptide growth inhibitory activity (p<0.02) and reduced the percentage of apoptotic cells from 32±4% to 20±5% (p<0.05). In conclusion, our results suggest that STAT1, STAT3 and p38 MAPK are mediating the antiproliferative activity and the apoptotic response triggered by the cyclic peptide in WISH cells, supporting this chimera as a novel agent potentially useful for cancer therapy.