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A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity

BACKGROUND: Based on its role in angiogenesis and apoptosis, the inhibition of NFκB activity is considered an effective treatment for cancer, hampered by the lack of selective and safe inhibitors. We recently demonstrated that the RH domain of GRK5 (GRK5-RH) inhibits NFκB, thus we evaluated its effe...

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Autores principales: Sorriento, Daniela, Campanile, Alfonso, Santulli, Gaetano, Leggiero, Eleonora, Pastore, Lucio, Trimarco, Bruno, Iaccarino, Guido
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780391/
https://www.ncbi.nlm.nih.gov/pubmed/19900276
http://dx.doi.org/10.1186/1476-4598-8-97
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author Sorriento, Daniela
Campanile, Alfonso
Santulli, Gaetano
Leggiero, Eleonora
Pastore, Lucio
Trimarco, Bruno
Iaccarino, Guido
author_facet Sorriento, Daniela
Campanile, Alfonso
Santulli, Gaetano
Leggiero, Eleonora
Pastore, Lucio
Trimarco, Bruno
Iaccarino, Guido
author_sort Sorriento, Daniela
collection PubMed
description BACKGROUND: Based on its role in angiogenesis and apoptosis, the inhibition of NFκB activity is considered an effective treatment for cancer, hampered by the lack of selective and safe inhibitors. We recently demonstrated that the RH domain of GRK5 (GRK5-RH) inhibits NFκB, thus we evaluated its effects on cancer growth. METHODS: The role of GRK5-RH on tumor growth was assessed in a human cancer cell line (KAT-4). RH overexpression was induced by adenovirus mediated gene transfer; alternatively we administered a synthetic protein reproducing the RH domain of GRK5 (TAT-RH), actively transported into the cells. RESULTS: In vitro, adenovirus mediated GRK5-RH overexpression (AdGRK5-NT) in human tumor cells (KAT-4) induces IκB accumulation and inhibits NFκB transcriptional activity leading to apoptotic events. In BALB/c nude mice harboring KAT-4 induced neoplasias, intra-tumor delivery of AdGRK5-NT reduces in a dose-dependent fashion tumor growth, with the highest doses completely inhibiting it. This phenomenon is paralleled by a decrease of NFκB activity, an increase of IκB levels and apoptotic events. To move towards a pharmacological setup, we synthesized the TAT-RH protein. In cultured KAT-4 cells, different dosages of TAT-RH reduced cell survival and increased apoptosis. In BALB/c mice, the anti-proliferative effects of TAT-RH appear to be dose-dependent and highest dose completely inhibits tumor growth. CONCLUSION: Our data suggest that GRK5-RH inhibition of NFκB is a novel and effective anti-tumoral strategy and TAT-RH could be an useful tool in the fighting of cancer.
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spelling pubmed-27803912009-11-21 A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity Sorriento, Daniela Campanile, Alfonso Santulli, Gaetano Leggiero, Eleonora Pastore, Lucio Trimarco, Bruno Iaccarino, Guido Mol Cancer Research BACKGROUND: Based on its role in angiogenesis and apoptosis, the inhibition of NFκB activity is considered an effective treatment for cancer, hampered by the lack of selective and safe inhibitors. We recently demonstrated that the RH domain of GRK5 (GRK5-RH) inhibits NFκB, thus we evaluated its effects on cancer growth. METHODS: The role of GRK5-RH on tumor growth was assessed in a human cancer cell line (KAT-4). RH overexpression was induced by adenovirus mediated gene transfer; alternatively we administered a synthetic protein reproducing the RH domain of GRK5 (TAT-RH), actively transported into the cells. RESULTS: In vitro, adenovirus mediated GRK5-RH overexpression (AdGRK5-NT) in human tumor cells (KAT-4) induces IκB accumulation and inhibits NFκB transcriptional activity leading to apoptotic events. In BALB/c nude mice harboring KAT-4 induced neoplasias, intra-tumor delivery of AdGRK5-NT reduces in a dose-dependent fashion tumor growth, with the highest doses completely inhibiting it. This phenomenon is paralleled by a decrease of NFκB activity, an increase of IκB levels and apoptotic events. To move towards a pharmacological setup, we synthesized the TAT-RH protein. In cultured KAT-4 cells, different dosages of TAT-RH reduced cell survival and increased apoptosis. In BALB/c mice, the anti-proliferative effects of TAT-RH appear to be dose-dependent and highest dose completely inhibits tumor growth. CONCLUSION: Our data suggest that GRK5-RH inhibition of NFκB is a novel and effective anti-tumoral strategy and TAT-RH could be an useful tool in the fighting of cancer. BioMed Central 2009-11-09 /pmc/articles/PMC2780391/ /pubmed/19900276 http://dx.doi.org/10.1186/1476-4598-8-97 Text en Copyright ©2009 Sorriento et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Sorriento, Daniela
Campanile, Alfonso
Santulli, Gaetano
Leggiero, Eleonora
Pastore, Lucio
Trimarco, Bruno
Iaccarino, Guido
A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity
title A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity
title_full A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity
title_fullStr A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity
title_full_unstemmed A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity
title_short A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity
title_sort new synthetic protein, tat-rh, inhibits tumor growth through the regulation of nfκb activity
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780391/
https://www.ncbi.nlm.nih.gov/pubmed/19900276
http://dx.doi.org/10.1186/1476-4598-8-97
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