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Title: Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on proliferation in brain tumor cell models

Abstract

Highlights: {yields} The histone deacetylase inhibitor 4-phenylbutyrate substantially enhance efficacy of the receptor tyrosine kinase inhibitors gefitinib or vandetanib in glioma and medulloblastoma cell lines. {yields} Cell death increases and clonogenic survival is reduced in the combination treatments, over mono-therapy. {yields} Combination treatments with these drugs may improve clinical outcome for cancer therapy. -- Abstract: We have investigated in vitro effects of anticancer therapy with the histone deacetylase inhibitor (HDACi) 4-phenylbutyrate (4-PB) combined with receptor tyrosine kinase inhibitors (RTKi) gefitinib or vandetanib on the survival of glioblastoma (U343MGa) and medulloblastoma (D324Med) cells. In comparison with individual effects of these drugs, combined treatment with gefitinib/4-PB or vandetanib/4-PB resulted in enhanced cell killing and reduced clonogenic survival in both cell lines. Our results suggest that combined treatment using HDACi and RTKi may beneficially affect the outcome of cancer therapy.

Authors:
 [1];  [2];  [3];  [2];  [2]; ;  [4];  [3];  [2];  [1];  [2];  [1];  [2]
  1. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden)
  2. (Sweden)
  3. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden)
  4. Department of Women's and Children's Health, Karolinska Institutet, Stockholm (Sweden)
Publication Date:
OSTI Identifier:
22207412
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 411; Journal Issue: 1; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BRAIN; CELL KILLING; CELL PROLIFERATION; DRUGS; GLIOMAS; IN VITRO; RECEPTORS; THERAPY; TUMOR CELLS; TYROSINE

Citation Formats

Marino, Ana-Maria, Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm, Sofiadis, Anastasios, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm, Baryawno, Ninib, Johnsen, John Inge, Larsson, Catharina, Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm, Vukojevic, Vladana, Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm, Ekstroem, Tomas J., E-mail: tomas.ekstrom@ki.se, and Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm. Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on proliferation in brain tumor cell models. United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2011.06.141.
Marino, Ana-Maria, Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm, Sofiadis, Anastasios, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm, Baryawno, Ninib, Johnsen, John Inge, Larsson, Catharina, Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm, Vukojevic, Vladana, Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm, Ekstroem, Tomas J., E-mail: tomas.ekstrom@ki.se, & Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm. Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on proliferation in brain tumor cell models. United States. doi:10.1016/J.BBRC.2011.06.141.
Marino, Ana-Maria, Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm, Sofiadis, Anastasios, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm, Baryawno, Ninib, Johnsen, John Inge, Larsson, Catharina, Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm, Vukojevic, Vladana, Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm, Ekstroem, Tomas J., E-mail: tomas.ekstrom@ki.se, and Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm. 2011. "Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on proliferation in brain tumor cell models". United States. doi:10.1016/J.BBRC.2011.06.141.
@article{osti_22207412,
title = {Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on proliferation in brain tumor cell models},
author = {Marino, Ana-Maria and Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm and Sofiadis, Anastasios and Department of Oncology-Pathology, Karolinska Institutet, Stockholm and Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm and Baryawno, Ninib and Johnsen, John Inge and Larsson, Catharina and Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm and Vukojevic, Vladana and Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm and Ekstroem, Tomas J., E-mail: tomas.ekstrom@ki.se and Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm},
abstractNote = {Highlights: {yields} The histone deacetylase inhibitor 4-phenylbutyrate substantially enhance efficacy of the receptor tyrosine kinase inhibitors gefitinib or vandetanib in glioma and medulloblastoma cell lines. {yields} Cell death increases and clonogenic survival is reduced in the combination treatments, over mono-therapy. {yields} Combination treatments with these drugs may improve clinical outcome for cancer therapy. -- Abstract: We have investigated in vitro effects of anticancer therapy with the histone deacetylase inhibitor (HDACi) 4-phenylbutyrate (4-PB) combined with receptor tyrosine kinase inhibitors (RTKi) gefitinib or vandetanib on the survival of glioblastoma (U343MGa) and medulloblastoma (D324Med) cells. In comparison with individual effects of these drugs, combined treatment with gefitinib/4-PB or vandetanib/4-PB resulted in enhanced cell killing and reduced clonogenic survival in both cell lines. Our results suggest that combined treatment using HDACi and RTKi may beneficially affect the outcome of cancer therapy.},
doi = {10.1016/J.BBRC.2011.06.141},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 411,
place = {United States},
year = 2011,
month = 7
}
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