Abstract
Interferons (IFNs) are proteins of the family of cytokines. Their antiproliferative function has been taken into account for several clinical therapies against malignant diseases. In this family, IFNs α and γ have demonstrated the highest antitumor effects. HerberPAG® is a new co-formulation with IFNs, α2b and γ. It has been obtained to increase the antiproliferative effect of individual IFNs and decrease their associated toxicity. Glioblastoma multiforme (GBM) is the most common primary brain tumor and one of the most deadly forms of cancer. The objective of the present work is to obtain insights into the regulation of Interferon-STAT-pathways and apoptosis in U87MG, at the transcriptional level. As a pharmacogenomic strategy we quantified mRNAs levels in vitro by quantitative PCR, using the cell line U87MG as a model. Some of the genes involved in the first steps of IFNs signaling pathways (stat1 and stat3) and apoptosis events (tp53, bax, bcl-2, bad, caspase3 (casp3), caspase8 (casp8) and caspase9 (casp9)) were studied. The detected mRNAs expression pattern for stat1and stat3 indicates a higher tumor suppressor activity of HerberPAG® compared to individuals IFNs. The up-regulation of tp53, bax, bad, casp3, casp8 and casp9 genes and the down regulation of bcl-2 gen, after the treatment with HerberPAG® show a pro-apoptotic function. HerberPAG® gene-induced profile shows an advantage in relation to IFN α2b and γ with a higher stat1 expression and a downregulation of bcl-2 which increases bax:bcl-2 ratio. The regulation of genes involved in IFN-STAT-pathways and apoptosis may be the first evidences to explain the increased antiproliferative properties of this co-formulation.
Keywords: Interferons, herberPAG®, antiproliferative, glioblastoma multiforme, pharmacogenomics.
Current Topics in Medicinal Chemistry
Title:Regulation by IFN-α/IFN-γ Co-Formulation (HerberPAG®) of Genes Involved in Interferon-STAT-Pathways and Apoptosis in U87MG
Volume: 14 Issue: 3
Author(s): Claudia Bello, Dania Vazquez-Blomquist, Jamilet Miranda, Yanelda Garcia, Lidia Ines Novoa, Daniel Palenzuela and Iraldo Bello
Affiliation:
Keywords: Interferons, herberPAG®, antiproliferative, glioblastoma multiforme, pharmacogenomics.
Abstract: Interferons (IFNs) are proteins of the family of cytokines. Their antiproliferative function has been taken into account for several clinical therapies against malignant diseases. In this family, IFNs α and γ have demonstrated the highest antitumor effects. HerberPAG® is a new co-formulation with IFNs, α2b and γ. It has been obtained to increase the antiproliferative effect of individual IFNs and decrease their associated toxicity. Glioblastoma multiforme (GBM) is the most common primary brain tumor and one of the most deadly forms of cancer. The objective of the present work is to obtain insights into the regulation of Interferon-STAT-pathways and apoptosis in U87MG, at the transcriptional level. As a pharmacogenomic strategy we quantified mRNAs levels in vitro by quantitative PCR, using the cell line U87MG as a model. Some of the genes involved in the first steps of IFNs signaling pathways (stat1 and stat3) and apoptosis events (tp53, bax, bcl-2, bad, caspase3 (casp3), caspase8 (casp8) and caspase9 (casp9)) were studied. The detected mRNAs expression pattern for stat1and stat3 indicates a higher tumor suppressor activity of HerberPAG® compared to individuals IFNs. The up-regulation of tp53, bax, bad, casp3, casp8 and casp9 genes and the down regulation of bcl-2 gen, after the treatment with HerberPAG® show a pro-apoptotic function. HerberPAG® gene-induced profile shows an advantage in relation to IFN α2b and γ with a higher stat1 expression and a downregulation of bcl-2 which increases bax:bcl-2 ratio. The regulation of genes involved in IFN-STAT-pathways and apoptosis may be the first evidences to explain the increased antiproliferative properties of this co-formulation.
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Cite this article as:
Bello Claudia, Vazquez-Blomquist Dania, Miranda Jamilet, Garcia Yanelda, Novoa Ines Lidia, Palenzuela Daniel and Bello Iraldo, Regulation by IFN-α/IFN-γ Co-Formulation (HerberPAG®) of Genes Involved in Interferon-STAT-Pathways and Apoptosis in U87MG, Current Topics in Medicinal Chemistry 2014; 14 (3) . https://dx.doi.org/10.2174/1568026613666131204125725
DOI https://dx.doi.org/10.2174/1568026613666131204125725 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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