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

Katherine E. Hanlon, Alysia N. Lozano-Ondoua, Puja J. Umaretiya, Ashley M. Symons-Liguori, Anupama Chandramouli, Jamie K. Moy, William K. Kwass, Patrick W. Mantyh, Mark A. Nelson, Todd W. Vanderah

Research output: Contribution to journalArticle

9 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)59-71
Number of pages13
JournalBreast Cancer: Targets and Therapy
Volume8
DOIs
StatePublished - Apr 15 2016

Keywords

  • Apoptosis
  • Breast cancer
  • CB
  • Calcium
  • Cannabinoid receptor-2
  • JWH-015
  • MAPK/ERK

ASJC Scopus subject areas

  • Oncology

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