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

Katherine E Hanlon,1,2 Alysia N Lozano-Ondoua,1 Puja J Umaretiya,1 Ashley M Symons-Liguori,1 Anupama Chandramouli,1 Jamie K Moy,1 William K Kwass,1 Patrick W Mantyh,1 Mark A Nelson,3 Todd W Vanderah,11Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA; 2Department...

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Autores principales:	Hanlon KE, Lozano-Ondoua AN, Umaretiya PJ, Symons-Liguori AM, Chandramouli A, Moy JK, Kwass WK, Mantyh PW, Nelson MA, Vanderah TW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	cannabinoid receptor-2 (CB2) breast cancer JWH-015 MAPK/ERK apoptosis calcium Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/fdc15611f19a4bba8d6361c18e48854b
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spelling	oai:doaj.org-article:fdc15611f19a4bba8d6361c18e48854b2021-12-02T01:27:53ZModulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent1179-1314https://doaj.org/article/fdc15611f19a4bba8d6361c18e48854b2016-04-01T00:00:00Zhttps://www.dovepress.com/modulation-of-breast-cancer-cell-viability-by-a-cannabinoid-receptor-2-peer-reviewed-article-BCTThttps://doaj.org/toc/1179-1314Katherine E Hanlon,1,2 Alysia N Lozano-Ondoua,1 Puja J Umaretiya,1 Ashley M Symons-Liguori,1 Anupama Chandramouli,1 Jamie K Moy,1 William K Kwass,1 Patrick W Mantyh,1 Mark A Nelson,3 Todd W Vanderah,11Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA; 2Department of Biomedical Sciences, University of New England College of Osteopathic Medicine, Biddeford, ME, USA; 3Department of Pathology, University of Arizona College of Medicine, Tucson, AZ, USA Introduction: Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB1) or cannabinoid receptor 2 (CB2), 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 CB1 and CB2 receptors may be distinct despite significant sequence homology and structural similarity of ligands. Methods: The CB2-selective agonist JWH-015 was used to investigate mechanisms downstream of CB2 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 Gαi signaling in vitro or modified by classical pharmacological blockade of CB1, 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 CB2-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.Keywords: cannabinoid receptor-2, CB2, breast cancer, JWH-015, MAPK/ERK, apoptosis, calcium Hanlon KELozano-Ondoua ANUmaretiya PJSymons-Liguori AMChandramouli AMoy JKKwass WKMantyh PWNelson MAVanderah TWDove Medical Pressarticlecannabinoid receptor-2 (CB2)breast cancerJWH-015MAPK/ERKapoptosiscalciumNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol 2016, Iss Issue 1, Pp 59-71 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	cannabinoid receptor-2 (CB2) breast cancer JWH-015 MAPK/ERK apoptosis calcium Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cannabinoid receptor-2 (CB2) breast cancer JWH-015 MAPK/ERK apoptosis calcium Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hanlon KE Lozano-Ondoua AN Umaretiya PJ Symons-Liguori AM Chandramouli A Moy JK Kwass WK Mantyh PW Nelson MA Vanderah TW Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent
description	Katherine E Hanlon,1,2 Alysia N Lozano-Ondoua,1 Puja J Umaretiya,1 Ashley M Symons-Liguori,1 Anupama Chandramouli,1 Jamie K Moy,1 William K Kwass,1 Patrick W Mantyh,1 Mark A Nelson,3 Todd W Vanderah,11Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA; 2Department of Biomedical Sciences, University of New England College of Osteopathic Medicine, Biddeford, ME, USA; 3Department of Pathology, University of Arizona College of Medicine, Tucson, AZ, USA Introduction: Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB1) or cannabinoid receptor 2 (CB2), 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 CB1 and CB2 receptors may be distinct despite significant sequence homology and structural similarity of ligands. Methods: The CB2-selective agonist JWH-015 was used to investigate mechanisms downstream of CB2 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 Gαi signaling in vitro or modified by classical pharmacological blockade of CB1, 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 CB2-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.Keywords: cannabinoid receptor-2, CB2, breast cancer, JWH-015, MAPK/ERK, apoptosis, calcium
format	article
author	Hanlon KE Lozano-Ondoua AN Umaretiya PJ Symons-Liguori AM Chandramouli A Moy JK Kwass WK Mantyh PW Nelson MA Vanderah TW
author_facet	Hanlon KE Lozano-Ondoua AN Umaretiya PJ Symons-Liguori AM Chandramouli A Moy JK Kwass WK Mantyh PW Nelson MA Vanderah TW
author_sort	Hanlon KE
title	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_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_sort	modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, jwh-015, is calcium dependent
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/fdc15611f19a4bba8d6361c18e48854b
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Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent

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