Synthetic Cannabinoid Agonist WIN 55212-2 Targets Proliferation, Angiogenesis, and Apoptosis via MAPK/AKT Signaling in Human Endometriotic Cell Lines and a Murine Model of Endometriosis

Harshavardhan Lingegowda; Jessica E Miller; Ryan M Marks; Lindsey K Symons; Taylor Alward; Alan E Lomax; Madhuri Koti; Chandrakant Tayade

doi:10.3389/frph.2021.726936

Synthetic Cannabinoid Agonist WIN 55212-2 Targets Proliferation, Angiogenesis, and Apoptosis via MAPK/AKT Signaling in Human Endometriotic Cell Lines and a Murine Model of Endometriosis

Front Reprod Health. 2021 Oct 5:3:726936. doi: 10.3389/frph.2021.726936. eCollection 2021.

Authors

Harshavardhan Lingegowda¹, Jessica E Miller¹, Ryan M Marks¹, Lindsey K Symons¹, Taylor Alward², Alan E Lomax², Madhuri Koti^{1

3

4}, Chandrakant Tayade¹

Affiliations

¹ Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
² Gastrointestinal Disease Research Unit (GIDRU), Queen's University, Kingston, ON, Canada.
³ Department of Obstetrics and Gynecology, Kingston General Hospital, Kingston, ON, Canada.
⁴ Division of Cancer Biology and Genetics, Queen's University, Kingston, ON, Canada.

Abstract

Endometriosis (EM) is characterized by the growth of endometrium-like tissue outside the uterus, leading to chronic inflammation and pelvic pain. Lesion proliferation, vascularization, and associated inflammation are the hallmark features of EM lesions. The legalization of recreational cannabinoids has garnered interest in the patient community and is contributing to a greater incidence of self medication; however, it remains unknown if cannabinoids possess marked disease-modifying properties. In this study, we assess the effects of synthetic cannabinoid, WIN 55212-2 (WIN 55), in EM-representative in vitro and in vivo syngeneic mouse models. WIN 55 reduced proliferation and angiogenesis in vitro, via MAPK/Akt-mediated apoptosis. These findings were corroborated in a mouse model of EM, where we found reduced TRPV1 expression in the dorsal root ganglia of the EM mouse model exposed to WIN 55, suggesting reduced signaling of pain stimuli. Ultimately, these pieces of evidence support the use of cannabinoid receptor agonists as a potential therapeutic intervention for EM associated pain and inflammation.

Keywords: angiogenesis; apoptosis; cannabinoids; endometriosis; inflammation.