Pegylated IFN-α sensitizes melanoma cells to chemotherapy and causes premature senescence in endothelial cells by IRF-1 mediated signaling.

ABSTRACT: Pegylated Interferon-α2b (pIFN-α) is an integral part of the drug regimen currently employed against melanoma. Interferon Regulatory Factor-1 (IRF-1) plays an important role in the transcriptional regulation of the IFN response, cell cycle and apoptosis. We have studied pIFN-α induced responses when combined with the chemotherapy agent, vinblastine in tumor and endothelial cell lines and the connection to IRF-1 signaling. Levels of IRF-1/IRF-2 protein expression were found to be decreased in tumor versus normal tissues. pIFN-α induced IRF-1 signaling in human melanoma (M14) and endothelial (EA.hy926) cells and enhanced cell death when combined with vinblastine. Upon combined IFN-α and vinblastine treatment, p21 expression, PARP cleavage and activated Bak levels were increased in M14 cells.

SUBMITTER: Upreti M 

PROVIDER: S-EPMC3010727 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature