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Research Paper
A Cyclic Chimeric Interferon-α2b Peptide Induces Apoptosis in Tumor Cells
Viviana C. Blank, Clara Peña and Leonor P. Roguin
volume 6 | issue 11
November 2007Pages: 1787 - 1793
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Interferons alpha (IFNsα) are a family of related proteins exhibiting antiviral, antiproliferative and immunoregulatory activities. Although IFNsα have been widely employed for the pharmacological treatment of different types of cancer, the therapeutic efficacy occasionally can be diminished by the appearance of side effects, neutralizing antibodies or tumor resistance. In the search of mimetic peptides of the IFN-α2b molecule, we have recently synthesized a chimeric cyclic peptide that inhibits IFN-α2b binding to its receptor and exerts an IFN-like antiproliferative activity. In order to study the mechanism of growth inhibition of the cyclic chimera, we evaluated its ability to induce cell cycle arrest or apoptosis in WISH cells. We found that the chimeric peptide did not cause a cell cycle arrest, although the entire IFN-α2b molecule did modify cell cycle by increasing the number of S-phase cells. In spite of this difference, both molecules were able to induce apoptosis through the activation of caspases 8 and 9, indicating the involvement of death receptor and mitochondrial pathways. In addition, both peptidic derivative and IFN-α2b altered the expression of Bcl-2 family proteins and induced the release of cytochrome C to cytosol, supporting the participation of mitochondrial pathway in the induction of apoptosis. In conclusion, we demonstrated that the chimeric cyclic peptide behaved as a potent inducer of apoptosis and it could be a potentially useful agent for the treatment of certain malignancies.
Authors
Viviana C. Blank
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET)
Clara Peña
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET)
Leonor P. Roguin
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET)
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.