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New Anti-Leukemic Effect of Carvacrol and Thymol Combination through Synergistic Induction of Different Cell Death Pathways
Acute myeloid leukemia (AML) is a cancer of the myeloid lineage of blood cells, and treatment for AML is lengthy and can be very expensive. Medicinal plants and their bioactive molecules are potential candidates for improving human health. In this work, we studied the effect of Ptychotis verticillat...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829697/ https://www.ncbi.nlm.nih.gov/pubmed/33466806 http://dx.doi.org/10.3390/molecules26020410 |
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author | Bouhtit, Fatima Najar, Mehdi Moussa Agha, Douâa Melki, Rahma Najimi, Mustapha Sadki, Khalid Boukhatem, Noureddine Bron, Dominique Meuleman, Nathalie Hamal, Abdellah Lagneaux, Laurence Lewalle, Philippe Merimi, Makram |
author_facet | Bouhtit, Fatima Najar, Mehdi Moussa Agha, Douâa Melki, Rahma Najimi, Mustapha Sadki, Khalid Boukhatem, Noureddine Bron, Dominique Meuleman, Nathalie Hamal, Abdellah Lagneaux, Laurence Lewalle, Philippe Merimi, Makram |
author_sort | Bouhtit, Fatima |
collection | PubMed |
description | Acute myeloid leukemia (AML) is a cancer of the myeloid lineage of blood cells, and treatment for AML is lengthy and can be very expensive. Medicinal plants and their bioactive molecules are potential candidates for improving human health. In this work, we studied the effect of Ptychotis verticillata (PV) essential oil and its derivatives, carvacrol and thymol, in AML cell lines. We demonstrated that a combination of carvacrol and thymol induced tumor cell death with low toxicity on normal cells. Mechanistically, we highlighted that different molecular pathways, including apoptosis, oxidative, reticular stress, autophagy, and necrosis, are implicated in this potential synergistic effect. Using quantitative RT-PCR, Western blotting, and apoptosis inhibitors, we showed that cell death induced by the carvacrol and thymol combination is caspase-dependent in the HL60 cell line and caspase-independent in the other cell lines tested. Further investigations should focus on improving the manufacturing of these compounds and understanding their anti-tumoral mechanisms of action. These efforts will lead to an increase in the efficiency of the oncotherapy strategy regarding AML. |
format | Online Article Text |
id | pubmed-7829697 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78296972021-01-26 New Anti-Leukemic Effect of Carvacrol and Thymol Combination through Synergistic Induction of Different Cell Death Pathways Bouhtit, Fatima Najar, Mehdi Moussa Agha, Douâa Melki, Rahma Najimi, Mustapha Sadki, Khalid Boukhatem, Noureddine Bron, Dominique Meuleman, Nathalie Hamal, Abdellah Lagneaux, Laurence Lewalle, Philippe Merimi, Makram Molecules Article Acute myeloid leukemia (AML) is a cancer of the myeloid lineage of blood cells, and treatment for AML is lengthy and can be very expensive. Medicinal plants and their bioactive molecules are potential candidates for improving human health. In this work, we studied the effect of Ptychotis verticillata (PV) essential oil and its derivatives, carvacrol and thymol, in AML cell lines. We demonstrated that a combination of carvacrol and thymol induced tumor cell death with low toxicity on normal cells. Mechanistically, we highlighted that different molecular pathways, including apoptosis, oxidative, reticular stress, autophagy, and necrosis, are implicated in this potential synergistic effect. Using quantitative RT-PCR, Western blotting, and apoptosis inhibitors, we showed that cell death induced by the carvacrol and thymol combination is caspase-dependent in the HL60 cell line and caspase-independent in the other cell lines tested. Further investigations should focus on improving the manufacturing of these compounds and understanding their anti-tumoral mechanisms of action. These efforts will lead to an increase in the efficiency of the oncotherapy strategy regarding AML. MDPI 2021-01-14 /pmc/articles/PMC7829697/ /pubmed/33466806 http://dx.doi.org/10.3390/molecules26020410 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bouhtit, Fatima Najar, Mehdi Moussa Agha, Douâa Melki, Rahma Najimi, Mustapha Sadki, Khalid Boukhatem, Noureddine Bron, Dominique Meuleman, Nathalie Hamal, Abdellah Lagneaux, Laurence Lewalle, Philippe Merimi, Makram New Anti-Leukemic Effect of Carvacrol and Thymol Combination through Synergistic Induction of Different Cell Death Pathways |
title | New Anti-Leukemic Effect of Carvacrol and Thymol Combination through Synergistic Induction of Different Cell Death Pathways |
title_full | New Anti-Leukemic Effect of Carvacrol and Thymol Combination through Synergistic Induction of Different Cell Death Pathways |
title_fullStr | New Anti-Leukemic Effect of Carvacrol and Thymol Combination through Synergistic Induction of Different Cell Death Pathways |
title_full_unstemmed | New Anti-Leukemic Effect of Carvacrol and Thymol Combination through Synergistic Induction of Different Cell Death Pathways |
title_short | New Anti-Leukemic Effect of Carvacrol and Thymol Combination through Synergistic Induction of Different Cell Death Pathways |
title_sort | new anti-leukemic effect of carvacrol and thymol combination through synergistic induction of different cell death pathways |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829697/ https://www.ncbi.nlm.nih.gov/pubmed/33466806 http://dx.doi.org/10.3390/molecules26020410 |
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