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Apoptosis of t(14;18)-positive lymphoma cells by a Bcl-2 interacting small molecule
Overexpression of Bcl-2 protein occurs via both t(14;18)-dependent and independent mechanisms and contributes to the survival and chemoresistance of non-Hodgkin lymphomas. HA14–1 is a nonpeptidic organic small molecule, which has been shown to inhibit the interaction of Bcl-2 with Bax, thereby inter...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Springer-Verlag
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725288/ https://www.ncbi.nlm.nih.gov/pubmed/19669197 http://dx.doi.org/10.1007/s12308-009-0028-x |
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author | Abbott, David R. Abbott, Robert T. Jenson, Stephen D. Fillmore, G. Chris Elenitoba-Johnson, Kojo S. J. Lim, Megan S. |
author_facet | Abbott, David R. Abbott, Robert T. Jenson, Stephen D. Fillmore, G. Chris Elenitoba-Johnson, Kojo S. J. Lim, Megan S. |
author_sort | Abbott, David R. |
collection | PubMed |
description | Overexpression of Bcl-2 protein occurs via both t(14;18)-dependent and independent mechanisms and contributes to the survival and chemoresistance of non-Hodgkin lymphomas. HA14–1 is a nonpeptidic organic small molecule, which has been shown to inhibit the interaction of Bcl-2 with Bax, thereby interfering with the antiapoptotic function of Bcl-2. In this study, we sought to determine the in vitro efficacy of HA14–1 as a therapeutic agent for non-Hodgkin lymphomas expressing Bcl-2. Assessment of cell viability demonstrated that HA14–1 induced a dose- (IC(50) = 10 μM) and time-dependent growth inhibition of a cell line (SudHL-4) derived from a t(14;18)-positive, Bcl-2-positive, non-Hodgkin lymphoma. HA14–1 effectively induced apoptosis via a caspase 3-mediated pathway but did not affect either the p38 MAPK or p44/42 MAPK pathways. Western blot analyses of Bcl-2 family proteins and other cell cycle-associated proteins were performed to determine the molecular sequelae of HA14–1-induced apoptosis. The results show down-regulation of Mcl-1 but up-regulation of p27(kip1), Bad, Bcl-xL, and Bcl-2 proteins, without change in Bax levels during HA14–1-mediated apoptosis. Our findings further elucidate the cellular mechanisms accompanying Bcl-2 inhibition and demonstrate the potential of Bcl-2 inhibitors as therapeutic agents for the treatment of non-Hodgkin lymphomas. |
format | Text |
id | pubmed-2725288 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-27252882009-08-13 Apoptosis of t(14;18)-positive lymphoma cells by a Bcl-2 interacting small molecule Abbott, David R. Abbott, Robert T. Jenson, Stephen D. Fillmore, G. Chris Elenitoba-Johnson, Kojo S. J. Lim, Megan S. J Hematop Original Article Overexpression of Bcl-2 protein occurs via both t(14;18)-dependent and independent mechanisms and contributes to the survival and chemoresistance of non-Hodgkin lymphomas. HA14–1 is a nonpeptidic organic small molecule, which has been shown to inhibit the interaction of Bcl-2 with Bax, thereby interfering with the antiapoptotic function of Bcl-2. In this study, we sought to determine the in vitro efficacy of HA14–1 as a therapeutic agent for non-Hodgkin lymphomas expressing Bcl-2. Assessment of cell viability demonstrated that HA14–1 induced a dose- (IC(50) = 10 μM) and time-dependent growth inhibition of a cell line (SudHL-4) derived from a t(14;18)-positive, Bcl-2-positive, non-Hodgkin lymphoma. HA14–1 effectively induced apoptosis via a caspase 3-mediated pathway but did not affect either the p38 MAPK or p44/42 MAPK pathways. Western blot analyses of Bcl-2 family proteins and other cell cycle-associated proteins were performed to determine the molecular sequelae of HA14–1-induced apoptosis. The results show down-regulation of Mcl-1 but up-regulation of p27(kip1), Bad, Bcl-xL, and Bcl-2 proteins, without change in Bax levels during HA14–1-mediated apoptosis. Our findings further elucidate the cellular mechanisms accompanying Bcl-2 inhibition and demonstrate the potential of Bcl-2 inhibitors as therapeutic agents for the treatment of non-Hodgkin lymphomas. Springer-Verlag 2009-02-28 /pmc/articles/PMC2725288/ /pubmed/19669197 http://dx.doi.org/10.1007/s12308-009-0028-x Text en © Springer-Verlag 2009 |
spellingShingle | Original Article Abbott, David R. Abbott, Robert T. Jenson, Stephen D. Fillmore, G. Chris Elenitoba-Johnson, Kojo S. J. Lim, Megan S. Apoptosis of t(14;18)-positive lymphoma cells by a Bcl-2 interacting small molecule |
title | Apoptosis of t(14;18)-positive lymphoma cells by a Bcl-2 interacting small molecule |
title_full | Apoptosis of t(14;18)-positive lymphoma cells by a Bcl-2 interacting small molecule |
title_fullStr | Apoptosis of t(14;18)-positive lymphoma cells by a Bcl-2 interacting small molecule |
title_full_unstemmed | Apoptosis of t(14;18)-positive lymphoma cells by a Bcl-2 interacting small molecule |
title_short | Apoptosis of t(14;18)-positive lymphoma cells by a Bcl-2 interacting small molecule |
title_sort | apoptosis of t(14;18)-positive lymphoma cells by a bcl-2 interacting small molecule |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725288/ https://www.ncbi.nlm.nih.gov/pubmed/19669197 http://dx.doi.org/10.1007/s12308-009-0028-x |
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