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α-bisabolol Is an Effective Proapoptotic Agent against BCR-ABL(+) Cells in Synergism with Imatinib and Nilotinib
We showed that α-bisabolol is active against primary acute leukemia cells, including BCR-ABL(+) acute lymphoblastic leukemias (ALL). Here we studied the activity of α-bisabolol against BCR-ABL(+) cells using 3 cell lines (K562, LAMA-84, CML-T1) and 10 primary BCR-ABL(+) ALL samples. We found that: (...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463553/ https://www.ncbi.nlm.nih.gov/pubmed/23056396 http://dx.doi.org/10.1371/journal.pone.0046674 |
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author | Bonifacio, Massimiliano Rigo, Antonella Guardalben, Emanuele Bergamini, Christian Cavalieri, Elisabetta Fato, Romana Pizzolo, Giovanni Suzuki, Hisanori Vinante, Fabrizio |
author_facet | Bonifacio, Massimiliano Rigo, Antonella Guardalben, Emanuele Bergamini, Christian Cavalieri, Elisabetta Fato, Romana Pizzolo, Giovanni Suzuki, Hisanori Vinante, Fabrizio |
author_sort | Bonifacio, Massimiliano |
collection | PubMed |
description | We showed that α-bisabolol is active against primary acute leukemia cells, including BCR-ABL(+) acute lymphoblastic leukemias (ALL). Here we studied the activity of α-bisabolol against BCR-ABL(+) cells using 3 cell lines (K562, LAMA-84, CML-T1) and 10 primary BCR-ABL(+) ALL samples. We found that: (a) α-bisabolol was effective in reducing BCR-ABL(+) cell viabilty at concentrations ranging from 53 to 73 µM; (b) α-bisabolol concentrations in BCR-ABL(+) cellular compartments were 4- to 12-fold higher than in normal cells, thus indicating a preferential intake in neoplastic cells; (c) α-bisabolol displayed a slight to strong synergism with the Tyrosine Kinase Inhibitors (TKI) imatinib and nilotinib: the combination of α-bisabolol+imatinib allowed a dose reduction of each compound up to 7.2 and 9.4-fold respectively, while the combination of α-bisabolol+nilotinib up to 6.7 and 5-fold respectively; (d) α-bisabolol-induced apoptosis was associated with loss of plasma membrane integrity, irreversible opening of mitochondrial transition pore, disruption of mitochondrial potential, inhibition of oxygen consumption and increase of intracellular reactive oxygen species. These data indicate α-bisabolol as a candidate for treatment of BCR-ABL(+) leukemias to overcome resistance to TKI alone and to target leukemic cells through BCR-ABL-independent pathways. |
format | Online Article Text |
id | pubmed-3463553 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34635532012-10-09 α-bisabolol Is an Effective Proapoptotic Agent against BCR-ABL(+) Cells in Synergism with Imatinib and Nilotinib Bonifacio, Massimiliano Rigo, Antonella Guardalben, Emanuele Bergamini, Christian Cavalieri, Elisabetta Fato, Romana Pizzolo, Giovanni Suzuki, Hisanori Vinante, Fabrizio PLoS One Research Article We showed that α-bisabolol is active against primary acute leukemia cells, including BCR-ABL(+) acute lymphoblastic leukemias (ALL). Here we studied the activity of α-bisabolol against BCR-ABL(+) cells using 3 cell lines (K562, LAMA-84, CML-T1) and 10 primary BCR-ABL(+) ALL samples. We found that: (a) α-bisabolol was effective in reducing BCR-ABL(+) cell viabilty at concentrations ranging from 53 to 73 µM; (b) α-bisabolol concentrations in BCR-ABL(+) cellular compartments were 4- to 12-fold higher than in normal cells, thus indicating a preferential intake in neoplastic cells; (c) α-bisabolol displayed a slight to strong synergism with the Tyrosine Kinase Inhibitors (TKI) imatinib and nilotinib: the combination of α-bisabolol+imatinib allowed a dose reduction of each compound up to 7.2 and 9.4-fold respectively, while the combination of α-bisabolol+nilotinib up to 6.7 and 5-fold respectively; (d) α-bisabolol-induced apoptosis was associated with loss of plasma membrane integrity, irreversible opening of mitochondrial transition pore, disruption of mitochondrial potential, inhibition of oxygen consumption and increase of intracellular reactive oxygen species. These data indicate α-bisabolol as a candidate for treatment of BCR-ABL(+) leukemias to overcome resistance to TKI alone and to target leukemic cells through BCR-ABL-independent pathways. Public Library of Science 2012-10-03 /pmc/articles/PMC3463553/ /pubmed/23056396 http://dx.doi.org/10.1371/journal.pone.0046674 Text en © 2012 Bonifacio et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Bonifacio, Massimiliano Rigo, Antonella Guardalben, Emanuele Bergamini, Christian Cavalieri, Elisabetta Fato, Romana Pizzolo, Giovanni Suzuki, Hisanori Vinante, Fabrizio α-bisabolol Is an Effective Proapoptotic Agent against BCR-ABL(+) Cells in Synergism with Imatinib and Nilotinib |
title | α-bisabolol Is an Effective Proapoptotic Agent against BCR-ABL(+) Cells in Synergism with Imatinib and Nilotinib |
title_full | α-bisabolol Is an Effective Proapoptotic Agent against BCR-ABL(+) Cells in Synergism with Imatinib and Nilotinib |
title_fullStr | α-bisabolol Is an Effective Proapoptotic Agent against BCR-ABL(+) Cells in Synergism with Imatinib and Nilotinib |
title_full_unstemmed | α-bisabolol Is an Effective Proapoptotic Agent against BCR-ABL(+) Cells in Synergism with Imatinib and Nilotinib |
title_short | α-bisabolol Is an Effective Proapoptotic Agent against BCR-ABL(+) Cells in Synergism with Imatinib and Nilotinib |
title_sort | α-bisabolol is an effective proapoptotic agent against bcr-abl(+) cells in synergism with imatinib and nilotinib |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463553/ https://www.ncbi.nlm.nih.gov/pubmed/23056396 http://dx.doi.org/10.1371/journal.pone.0046674 |
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