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The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM
We have previously demonstrated that activation of the cyclic adenosine monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both in vitro and in vivo. In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the cA...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549684/ https://www.ncbi.nlm.nih.gov/pubmed/26306624 http://dx.doi.org/10.1038/srep13001 |
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author | Follin-Arbelet, Virginie Misund, Kristine Hallan Naderi, Elin Ugland, Hege Sundan, Anders Kiil Blomhoff, Heidi |
author_facet | Follin-Arbelet, Virginie Misund, Kristine Hallan Naderi, Elin Ugland, Hege Sundan, Anders Kiil Blomhoff, Heidi |
author_sort | Follin-Arbelet, Virginie |
collection | PubMed |
description | We have previously demonstrated that activation of the cyclic adenosine monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both in vitro and in vivo. In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the cAMP-elevating compound forskolin with the commonly used MM therapeutic drugs melphalan, cyclophosphamide, doxorubicin, bortezomib and dexamethasone. We observed that forskolin potentiated the killing induced by all the tested agents as compared to treatment with the single agents alone. In particular, forskolin had a synergistic effect on the dexamethasone-responsive cell lines H929 and OM-2. By knocking down the proapoptotic BCL-2 family member BIM, we proved this protein to be involved in the synergistic induction of apoptosis by dexamethasone and forskolin. The ability of forskolin to maintain the killing of MM cells even at lower concentrations of the conventional agents suggests that forskolin may be used to diminish treatment-associated side effects. Our findings support a potential role of forskolin in combination with current conventional agents in the treatment of MM. |
format | Online Article Text |
id | pubmed-4549684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45496842015-08-26 The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM Follin-Arbelet, Virginie Misund, Kristine Hallan Naderi, Elin Ugland, Hege Sundan, Anders Kiil Blomhoff, Heidi Sci Rep Article We have previously demonstrated that activation of the cyclic adenosine monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both in vitro and in vivo. In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the cAMP-elevating compound forskolin with the commonly used MM therapeutic drugs melphalan, cyclophosphamide, doxorubicin, bortezomib and dexamethasone. We observed that forskolin potentiated the killing induced by all the tested agents as compared to treatment with the single agents alone. In particular, forskolin had a synergistic effect on the dexamethasone-responsive cell lines H929 and OM-2. By knocking down the proapoptotic BCL-2 family member BIM, we proved this protein to be involved in the synergistic induction of apoptosis by dexamethasone and forskolin. The ability of forskolin to maintain the killing of MM cells even at lower concentrations of the conventional agents suggests that forskolin may be used to diminish treatment-associated side effects. Our findings support a potential role of forskolin in combination with current conventional agents in the treatment of MM. Nature Publishing Group 2015-08-26 /pmc/articles/PMC4549684/ /pubmed/26306624 http://dx.doi.org/10.1038/srep13001 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Follin-Arbelet, Virginie Misund, Kristine Hallan Naderi, Elin Ugland, Hege Sundan, Anders Kiil Blomhoff, Heidi The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM |
title | The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM |
title_full | The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM |
title_fullStr | The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM |
title_full_unstemmed | The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM |
title_short | The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM |
title_sort | natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via bim |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549684/ https://www.ncbi.nlm.nih.gov/pubmed/26306624 http://dx.doi.org/10.1038/srep13001 |
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