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 Lomax, Alan E Lomax, Madhuri Koti, Chandrakant Tayade
Frontiers in reproductive health · 2021 · vol. 3 , pp. 726936 · doi:10.3389/frph.2021.726936 · PMID:36304004 · PMC9580784 · W3202684981
article OA: gold CC0 ⤵ 9 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Synthetic cannabinoid WIN 55212-2 inhibited proliferation and angiogenesis via MAPK/Akt-mediated apoptosis in endometriotic cells and reduced pain signaling in a murine model.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 ⓘ

This study investigated the effects of the non-selective CB1/CB2 synthetic cannabinoid agonist WIN 55212-2 (WIN 55; mesylate) on proliferation, angiogenesis, apoptosis, and associated MAPK/Akt signaling in immortalized human endometriotic epithelial cells (12Z), immortalized human endometrial stromal cells (HESC), and human umbilical vein endothelial cells (HUVECs), using in vitro assays plus a syngeneic murine model of endometriosis. WIN 55 inhibited proliferation and angiogenesis and promoted apoptosis in a dose-dependent manner in vitro, and kinase array and related analyses indicated changes in MAPK and Akt signaling; in the mouse model, WIN 55 attenuated angiogenesis and proliferation and increased apoptosis in endometriosis-like lesions and altered TRPV1 expression in dorsal root ganglia. The paper’s caveats include that it used cell-line and model-based systems with WIN 55 delivered via an emulsion-based solvent, without describing patient-level variability or clinical endpoints. This paper is centrally about endometriosis — it tests WIN 55212-2 effects in human endometriotic cell lines and an endometriosis mouse model, linking cannabinoid receptor activation to MAPK/Akt, apoptosis, angiogenesis, and TRPV1 changes.

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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.

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endometriosis

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