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

Persistent Link:
http://hdl.handle.net/10150/614744
Title:
Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent
Author:
Vanderah, Todd; Hanlon, Katherine; Lozano-Ondoua, Alysia; Umaretiya, Puja; Symons-Ligouri, Ashley; Chandramouli, Anupama; Moy, Jamie; Kwass, William; Mantyh, Patrick; Nelson, Mark
Affiliation:
Univ Arizona, Coll Med, Dept Pharmacol; Univ Arizona, Coll Med, Dept Pathol
Issue Date:
2016-04
Publisher:
DOVE MEDICAL PRESS LTD
Citation:
Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent 2016:59 Breast Cancer: Targets and Therapy
Journal:
Breast Cancer: Targets and Therapy
Rights:
© 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/).
Collection Information:
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
Abstract:
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 G alpha(i) 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.
ISSN:
1179-1314
DOI:
10.2147/BCTT.S100393
Keywords:
cannabinoid receptor-2; CB2; breast cancer; JWH-015; MAPK/ERK; apoptosis; calcium
Version:
Final published version
Additional Links:
https://www.dovepress.com/modulation-of-breast-cancer-cell-viability-by-a-cannabinoid-receptor-2-peer-reviewed-article-BCTT

Full metadata record

DC FieldValue Language
dc.contributor.authorVanderah, Todden
dc.contributor.authorHanlon, Katherineen
dc.contributor.authorLozano-Ondoua, Alysiaen
dc.contributor.authorUmaretiya, Pujaen
dc.contributor.authorSymons-Ligouri, Ashleyen
dc.contributor.authorChandramouli, Anupamaen
dc.contributor.authorMoy, Jamieen
dc.contributor.authorKwass, Williamen
dc.contributor.authorMantyh, Patricken
dc.contributor.authorNelson, Marken
dc.date.accessioned2016-06-24T23:07:10Z-
dc.date.available2016-06-24T23:07:10Z-
dc.date.issued2016-04-
dc.identifier.citationModulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent 2016:59 Breast Cancer: Targets and Therapyen
dc.identifier.issn1179-1314-
dc.identifier.doi10.2147/BCTT.S100393-
dc.identifier.urihttp://hdl.handle.net/10150/614744-
dc.description.abstractIntroduction: 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 G alpha(i) 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.en
dc.language.isoenen
dc.publisherDOVE MEDICAL PRESS LTDen
dc.relation.urlhttps://www.dovepress.com/modulation-of-breast-cancer-cell-viability-by-a-cannabinoid-receptor-2-peer-reviewed-article-BCTTen
dc.rights© 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/).en
dc.subjectcannabinoid receptor-2en
dc.subjectCB2en
dc.subjectbreast canceren
dc.subjectJWH-015en
dc.subjectMAPK/ERKen
dc.subjectapoptosisen
dc.subjectcalciumen
dc.titleModulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependenten
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Coll Med, Dept Pharmacolen
dc.contributor.departmentUniv Arizona, Coll Med, Dept Patholen
dc.identifier.journalBreast Cancer: Targets and Therapyen
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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