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FAAH inhibition ameliorates breast cancer in a murine model

Breast cancer is the leading cancer among females worldwide. Disease outcome depends on the hormonal status of the cancer and whether or not it is metastatic, but there is a need for more efficacious therapeutic strategies where first line treatment fails. In this study, Fatty Acid Amide Hydrolase (...

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Autores principales: Tripathy, Mallika, Bui, Amy, Henderson, Jared, Sun, Jeffrey, Woods, Christian Rutan, Somani, Soumya, Doan, Thao, Louis Sam Titus, Anto Sam Crosslee, Mohan, Chandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624203/
https://www.ncbi.nlm.nih.gov/pubmed/37921652
http://dx.doi.org/10.18632/oncotarget.28534
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author Tripathy, Mallika
Bui, Amy
Henderson, Jared
Sun, Jeffrey
Woods, Christian Rutan
Somani, Soumya
Doan, Thao
Louis Sam Titus, Anto Sam Crosslee
Mohan, Chandra
author_facet Tripathy, Mallika
Bui, Amy
Henderson, Jared
Sun, Jeffrey
Woods, Christian Rutan
Somani, Soumya
Doan, Thao
Louis Sam Titus, Anto Sam Crosslee
Mohan, Chandra
author_sort Tripathy, Mallika
collection PubMed
description Breast cancer is the leading cancer among females worldwide. Disease outcome depends on the hormonal status of the cancer and whether or not it is metastatic, but there is a need for more efficacious therapeutic strategies where first line treatment fails. In this study, Fatty Acid Amide Hydrolase (FAAH) inhibition and endocannabinoids were examined as therapeutic alternatives. FAAH is an integral membrane enzyme that hydrolyzes endocannabinoids, rendering them inactive, and FAAH inhibition is predicted to increase cancer cell death. To test this, breast cancer cells were probed for FAAH expression using Western blot analysis, treated with FAAH inhibitors, exogenous endocannabinoids, and combinations of the two treatments, and assessed for viability. High levels of FAAH were observed in different breast cancer cell lines. FAAH inhibition was more effective than exogenous endocannabinoid treatment, and the combination of FAAH inhibitors and endocannabinoids was the most effective in inducing apoptosis of breast cancer cells in vitro. In addition, in vivo FAAH inhibition reduced breast cancer growth in immunodeficient mice. FAAH inhibition is a promising approach, and tremendous progress has been made in the field to validate this mechanism as an alternative to chemotherapy. Further research exploring the therapeutic potential and impact of FAAH expression on cancer cells is warranted.
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spelling pubmed-106242032023-11-04 FAAH inhibition ameliorates breast cancer in a murine model Tripathy, Mallika Bui, Amy Henderson, Jared Sun, Jeffrey Woods, Christian Rutan Somani, Soumya Doan, Thao Louis Sam Titus, Anto Sam Crosslee Mohan, Chandra Oncotarget Research Paper Breast cancer is the leading cancer among females worldwide. Disease outcome depends on the hormonal status of the cancer and whether or not it is metastatic, but there is a need for more efficacious therapeutic strategies where first line treatment fails. In this study, Fatty Acid Amide Hydrolase (FAAH) inhibition and endocannabinoids were examined as therapeutic alternatives. FAAH is an integral membrane enzyme that hydrolyzes endocannabinoids, rendering them inactive, and FAAH inhibition is predicted to increase cancer cell death. To test this, breast cancer cells were probed for FAAH expression using Western blot analysis, treated with FAAH inhibitors, exogenous endocannabinoids, and combinations of the two treatments, and assessed for viability. High levels of FAAH were observed in different breast cancer cell lines. FAAH inhibition was more effective than exogenous endocannabinoid treatment, and the combination of FAAH inhibitors and endocannabinoids was the most effective in inducing apoptosis of breast cancer cells in vitro. In addition, in vivo FAAH inhibition reduced breast cancer growth in immunodeficient mice. FAAH inhibition is a promising approach, and tremendous progress has been made in the field to validate this mechanism as an alternative to chemotherapy. Further research exploring the therapeutic potential and impact of FAAH expression on cancer cells is warranted. Impact Journals LLC 2023-10-31 /pmc/articles/PMC10624203/ /pubmed/37921652 http://dx.doi.org/10.18632/oncotarget.28534 Text en Copyright: © 2023 Tripathy et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Tripathy, Mallika
Bui, Amy
Henderson, Jared
Sun, Jeffrey
Woods, Christian Rutan
Somani, Soumya
Doan, Thao
Louis Sam Titus, Anto Sam Crosslee
Mohan, Chandra
FAAH inhibition ameliorates breast cancer in a murine model
title FAAH inhibition ameliorates breast cancer in a murine model
title_full FAAH inhibition ameliorates breast cancer in a murine model
title_fullStr FAAH inhibition ameliorates breast cancer in a murine model
title_full_unstemmed FAAH inhibition ameliorates breast cancer in a murine model
title_short FAAH inhibition ameliorates breast cancer in a murine model
title_sort faah inhibition ameliorates breast cancer in a murine model
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624203/
https://www.ncbi.nlm.nih.gov/pubmed/37921652
http://dx.doi.org/10.18632/oncotarget.28534
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