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Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent

INTRODUCTION: Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB(1)) or cannabinoid receptor 2 (CB(2)), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems. The mechanism of this...

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Autores principales: Hanlon, Katherine E, Lozano-Ondoua, Alysia N, Umaretiya, Puja J, Symons-Liguori, Ashley M, Chandramouli, Anupama, Moy, Jamie K, Kwass, William K, Mantyh, Patrick W, Nelson, Mark A, Vanderah, Todd W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847606/
https://www.ncbi.nlm.nih.gov/pubmed/27186076
http://dx.doi.org/10.2147/BCTT.S100393
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author Hanlon, Katherine E
Lozano-Ondoua, Alysia N
Umaretiya, Puja J
Symons-Liguori, Ashley M
Chandramouli, Anupama
Moy, Jamie K
Kwass, William K
Mantyh, Patrick W
Nelson, Mark A
Vanderah, Todd W
author_facet Hanlon, Katherine E
Lozano-Ondoua, Alysia N
Umaretiya, Puja J
Symons-Liguori, Ashley M
Chandramouli, Anupama
Moy, Jamie K
Kwass, William K
Mantyh, Patrick W
Nelson, Mark A
Vanderah, Todd W
author_sort Hanlon, Katherine E
collection PubMed
description INTRODUCTION: Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB(1)) or cannabinoid receptor 2 (CB(2)), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems. The mechanism of this modulation remains only partially delineated, and activity induced via the CB(1) and CB(2) receptors may be distinct despite significant sequence homology and structural similarity of ligands. METHODS: The CB(2)-selective agonist JWH-015 was used to investigate mechanisms downstream of CB(2) activation in mouse and human breast cancer cell lines in vitro and in a murine mammary tumor model. RESULTS: JWH-015 treatment significantly reduced primary tumor burden and metastasis of luciferase-tagged murine mammary carcinoma 4T1 cells in immunocompetent mice in vivo. Furthermore, JWH-015 reduced the viability of murine 4T1 and human MCF7 mammary carcinoma cells in vitro by inducing apoptosis. JWH-015-mediated reduction of breast cancer cell viability was not dependent on Gα(i) signaling in vitro or modified by classical pharmacological blockade of CB(1), GPR55, TRPV1, or TRPA1 receptors. JWH-015 effects were calcium dependent and induced changes in MAPK/ERK signaling. CONCLUSION: The results of this work characterize the actions of a CB(2)-selective agonist on breast cancer cells in a syngeneic murine model representing how a clinical presentation of cancer progression and metastasis may be significantly modulated by a G-protein-coupled receptor.
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spelling pubmed-48476062016-05-16 Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent Hanlon, Katherine E Lozano-Ondoua, Alysia N Umaretiya, Puja J Symons-Liguori, Ashley M Chandramouli, Anupama Moy, Jamie K Kwass, William K Mantyh, Patrick W Nelson, Mark A Vanderah, Todd W Breast Cancer (Dove Med Press) Original Research INTRODUCTION: Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB(1)) or cannabinoid receptor 2 (CB(2)), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems. The mechanism of this modulation remains only partially delineated, and activity induced via the CB(1) and CB(2) receptors may be distinct despite significant sequence homology and structural similarity of ligands. METHODS: The CB(2)-selective agonist JWH-015 was used to investigate mechanisms downstream of CB(2) activation in mouse and human breast cancer cell lines in vitro and in a murine mammary tumor model. RESULTS: JWH-015 treatment significantly reduced primary tumor burden and metastasis of luciferase-tagged murine mammary carcinoma 4T1 cells in immunocompetent mice in vivo. Furthermore, JWH-015 reduced the viability of murine 4T1 and human MCF7 mammary carcinoma cells in vitro by inducing apoptosis. JWH-015-mediated reduction of breast cancer cell viability was not dependent on Gα(i) signaling in vitro or modified by classical pharmacological blockade of CB(1), GPR55, TRPV1, or TRPA1 receptors. JWH-015 effects were calcium dependent and induced changes in MAPK/ERK signaling. CONCLUSION: The results of this work characterize the actions of a CB(2)-selective agonist on breast cancer cells in a syngeneic murine model representing how a clinical presentation of cancer progression and metastasis may be significantly modulated by a G-protein-coupled receptor. Dove Medical Press 2016-04-15 /pmc/articles/PMC4847606/ /pubmed/27186076 http://dx.doi.org/10.2147/BCTT.S100393 Text en © 2016 Hanlon et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Hanlon, Katherine E
Lozano-Ondoua, Alysia N
Umaretiya, Puja J
Symons-Liguori, Ashley M
Chandramouli, Anupama
Moy, Jamie K
Kwass, William K
Mantyh, Patrick W
Nelson, Mark A
Vanderah, Todd W
Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent
title Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent
title_full Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent
title_fullStr Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent
title_full_unstemmed Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent
title_short Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent
title_sort modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, jwh-015, is calcium dependent
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847606/
https://www.ncbi.nlm.nih.gov/pubmed/27186076
http://dx.doi.org/10.2147/BCTT.S100393
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