Antiproliferative Effects of Cannabinoid Agonists on Deep Infiltrating Endometriosis

Leconte, Mahaut; Nicco, Carole; Ngô, Charlotte; Arkwright, S; Chéreau, Christiane; Gadrey, Jean; Weill, Bernard; Chapron, Charles; Dousset, B.; Batteux, Frédéric

doi:10.2353/ajpath.2010.100375

Cited by 72 publications

(58 citation statements)

References 45 publications

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“…Similar results were presented earlier by Leconte et al [102], who demonstrated an antiproliferative effect of the nonselective CB 1 /CB 2 agonist WIN 55212-2 on deep infiltrating endometrial stromal cells. This effect was a result of inactivation of the Akt pathway by WIN 55212-2 [102]. These in vitro results were confirmed by a mouse model of deep infiltrating endometriosis [102].…”

Section: The Ecs In Gynecological Disorders and Cancersupporting

confidence: 91%

“…The CB 2 -mediated effect was more prominent in Ishikawa cells while the CB 1 -mediated effect was more prominent in CLR-7566 cells [100]. Similar results were presented earlier by Leconte et al [102], who demonstrated an antiproliferative effect of the nonselective CB 1 /CB 2 agonist WIN 55212-2 on deep infiltrating endometrial stromal cells. This effect was a result of inactivation of the Akt pathway by WIN 55212-2 [102].…”

Section: The Ecs In Gynecological Disorders and Cancersupporting

confidence: 84%

“…This effect was a result of inactivation of the Akt pathway by WIN 55212-2 [102]. These in vitro results were confirmed by a mouse model of deep infiltrating endometriosis [102]. In contrast, Sanchez et al [103] found that selective activation of CB 1 by methanandamide was linked to the development of ectopic lesions in a mouse model of endometriosis.…”

Section: The Ecs In Gynecological Disorders and Cancermentioning

confidence: 92%

“…The discrepancies may be explained by the fact that there are basic differences in the animal models of endometriosis. Sanchez et al [103] used a model to elucidate the development of ectopic lesions in initial stages while Leconte et al [102] transplanted human endometriotic tissue into nude mice to investigate effects on already established lesions. Thus, species differences between the rodent and human endometrium may exist [102, 103].…”

Section: The Ecs In Gynecological Disorders and Cancermentioning

confidence: 99%

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Cannabinoids in Gynecological Diseases

Luschnig

Schicho

2019

Med Cannabis Cannabinoids

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The endocannabinoid system (ECS) is a multifunctional homeostatic system involved in many physiological and pathological conditions. The ligands of the ECS are the endocannabinoids, whose actions are mimicked by exogenous cannabinoids, such as phytocannabinoids and synthetic cannabinoids. Responses to the ligands of the ECS are mediated by numerous receptors like the classical cannabinoid receptors (CB1 and CB2) as well as ECS-related receptors, e.g., G protein-coupled receptors 18 and 55 (GPR18 and GPR55), transient receptor potential ion channels, and nuclear peroxisome proliferator-activated receptors. The ECS regulates almost all levels of female reproduction, starting with oocyte production through to parturition. Dysregulation of the ECS is associated with the development of gynecological disorders from fertility disorders to cancer. Cannabinoids that act at the ECS as specific agonists or antagonists may potentially influence dysregulation and, therefore, represent new therapeutic options for the therapy of gynecological disorders.

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Section: The Ecs In Gynecological Disorders and Cancersupporting

confidence: 91%

Section: The Ecs In Gynecological Disorders and Cancersupporting

confidence: 84%

Section: The Ecs In Gynecological Disorders and Cancermentioning

confidence: 92%

Section: The Ecs In Gynecological Disorders and Cancermentioning

confidence: 99%

See 2 more Smart Citations

Cannabinoids in Gynecological Diseases

Luschnig

Schicho

2019

Med Cannabis Cannabinoids

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“…Leconte et al (2010) showed that in vitro treatment with the agonist WIN 55212-2 has an antiproliferative effect mediated by a mechanism involving reduction of reactive oxygen species production and inactivation of the Akt pathway. Preliminary data from our laboratory confirm these findings.…”

Section: Endocannabinoid and The Uterusmentioning

confidence: 99%

The endocannabinoid pathway and the female reproductive organs

Blasio¹,

Vignali²,

Gentilini³

2012

Journal of Molecular Endocrinology

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Endocannabinoids are endogenous ligands of cannabinoid, vanilloid and peroxisome proliferator-activated receptors that activate multiple signal transduction pathways. Together with their receptor and the enzymes responsible for their synthesis and degradation, these compounds constitute the endocannabinoid system that has been recently shown to play, in humans, an important role in modulating several central and peripheral functions including reproduction. Given the relevance of the system, drugs that are able to interfere with the activity of endocannabinoids are currently considered as candidates for the treatment of various diseases. In this review, we will summarise the current knowledge regarding the effects of endocannabinoids in female reproductive organs. In particular, we will focus on some newly reported mechanisms that can affect endometrial plasticity both in physiological and in pathological conditions.

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Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review

Hung

Zhang

Tan

et al. 2021

Medicinal Research Reviews

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Endometriosis (EM) is defined as endometrial tissues found outside the uterus. Growth and development of endometriotic cells in ectopic sites can be promoted via multiple pathways, including MAPK/MEK/ERK, PI3K/Akt/mTOR, NF‐κB, Rho/ROCK, reactive oxidative stress, tumor necrosis factor, transforming growth factor‐β, Wnt/β‐catenin, vascular endothelial growth factor, estrogen, and cytokines. The underlying pathophysiological mechanisms include proliferation, apoptosis, autophagy, migration, invasion, fibrosis, angiogenesis, oxidative stress, inflammation, and immune escape. Current medical treatments for EM are mainly hormonal and symptomatic, and thus the development of new, effective, and safe pharmaceuticals targeting specific molecular and signaling pathways is needed. Here, we systematically reviewed the literature focused on pharmaceuticals that specifically target the molecular and signaling pathways involved in the pathophysiology of EM. Potential drug targets, their upstream and downstream molecules with key aberrant signaling, and the regulatory mechanisms promoting the growth and development of endometriotic cells and tissues were discussed. Hormonal pharmaceuticals, including melatonin, exerts proapoptotic via regulating matrix metallopeptidase activity while nonhormonal pharmaceutical sorafenib exerts antiproliferative effect via MAPK/ERK pathway and antiangiogenesis activity via VEGF/VEGFR pathway. N‐acetyl cysteine, curcumin, and ginsenoside exert antioxidant and anti‐inflammatory effects via radical scavenging activity. Natural products have high efficacy with minimal side effects; for example, resveratrol and epigallocatechin gallate have multiple targets and provide synergistic efficacy to resolve the complexity of the pathophysiology of EM, showing promising efficacy in treating EM. Although new medical treatments are currently being developed, more detailed pharmacological studies and large sample size clinical trials are needed to confirm the efficacy and safety of these treatments in the near future.

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Antiproliferative Effects of Cannabinoid Agonists on Deep Infiltrating Endometriosis

Abstract: Deep infiltrating endometriosis (DIE) is

Cited by 72 publications

References 45 publications

Cannabinoids in Gynecological Diseases

Cannabinoids in Gynecological Diseases

The endocannabinoid pathway and the female reproductive organs

Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review

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