Chronic Administration of Cannabinoid Receptor 2 Agonist (JWH-133) Increases Ectopic Ovarian Tumor Growth and Endocannabinoids (Anandamide and 2-Arachidonoyl Glycerol) Levels in Immunocompromised SCID Female Mice
Cannabinoid-based therapies are increasingly being used by cancer patients to treat chemotherapy-induced nausea and vomiting. Recently, cannabinoids have gained increased attention for their effects on cancer growth. Indeed, the effect of CB2 (JWH-015, JWH-133) agonists on breast cancer models have...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.823132/full |
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| author | Henry L. Blanton Melissa C. McHann Haley De Selle Canice Lei Dancel Jose-Luis Redondo Deborah Molehin Nadezhda A. German Scott Trasti Kevin Pruitt Isabel Castro-Piedras Josée Guindon Josée Guindon |
| author_facet | Henry L. Blanton Melissa C. McHann Haley De Selle Canice Lei Dancel Jose-Luis Redondo Deborah Molehin Nadezhda A. German Scott Trasti Kevin Pruitt Isabel Castro-Piedras Josée Guindon Josée Guindon |
| author_sort | Henry L. Blanton |
| collection | DOAJ |
| description | Cannabinoid-based therapies are increasingly being used by cancer patients to treat chemotherapy-induced nausea and vomiting. Recently, cannabinoids have gained increased attention for their effects on cancer growth. Indeed, the effect of CB2 (JWH-015, JWH-133) agonists on breast cancer models have shown to reduce the size of breast cancer tumors. However, these studies assessing breast cancer progression were using CB2 agonist administered early into the cancer progression therefore assessing their effects on already established tumors is a critical need. In our study, we evaluate tumor growth using an ectopic xenograft ovarian (SKOV-3 and OVCAR-5) cancer model. The impact of chronic (30 days) administration of CB2 (JWH-133) agonist will be evaluated and started on 30 days of ectopic ovarian tumors. We will then evaluate and determine the mechanisms involved in ovarian cancer tumor growth by measuring levels of anandamide and 2-arachidonoyl glycerol as well as protein levels of CB1, CB2, ERα, ERβ, GPER, TNFα, IL-1β and IL-6 in ovarian and tumor tissues. Our results demonstrate a significant increase in ectopic ovarian tumor growth following chronic administration of JWH-133. Ovarian cancer tumor tissues chronically (30 days) treated with JWH-133 in comparison to vehicle treated groups showed an increase in endocannabinoid (AEA and 2-AG) and protein (CB2 and TNFα) levels with a decrease in GPER protein levels. Interestingly, our study emphasizes the importance of studying the impact of cannabinoid compounds on already established tumors to improve our understanding of cannabinoid-based therapies and, therefore better address clinical needs in cancer patients. |
| first_indexed | 2024-12-13T00:38:34Z |
| format | Article |
| id | doaj.art-430f2198d6a444b48ecedc0c4ae931da |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T00:38:34Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-430f2198d6a444b48ecedc0c4ae931da2022-12-22T00:05:11ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-02-011310.3389/fphar.2022.823132823132Chronic Administration of Cannabinoid Receptor 2 Agonist (JWH-133) Increases Ectopic Ovarian Tumor Growth and Endocannabinoids (Anandamide and 2-Arachidonoyl Glycerol) Levels in Immunocompromised SCID Female MiceHenry L. Blanton0Melissa C. McHann1Haley De Selle2Canice Lei Dancel3Jose-Luis Redondo4Deborah Molehin5Nadezhda A. German6Scott Trasti7Kevin Pruitt8Isabel Castro-Piedras9Josée Guindon10Josée Guindon11Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesDepartment of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesDepartment of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesDepartment of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesDepartment of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesDepartment of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesDepartment of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesDepartment of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesDepartment of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesDepartment of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesDepartment of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesCenter of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesCannabinoid-based therapies are increasingly being used by cancer patients to treat chemotherapy-induced nausea and vomiting. Recently, cannabinoids have gained increased attention for their effects on cancer growth. Indeed, the effect of CB2 (JWH-015, JWH-133) agonists on breast cancer models have shown to reduce the size of breast cancer tumors. However, these studies assessing breast cancer progression were using CB2 agonist administered early into the cancer progression therefore assessing their effects on already established tumors is a critical need. In our study, we evaluate tumor growth using an ectopic xenograft ovarian (SKOV-3 and OVCAR-5) cancer model. The impact of chronic (30 days) administration of CB2 (JWH-133) agonist will be evaluated and started on 30 days of ectopic ovarian tumors. We will then evaluate and determine the mechanisms involved in ovarian cancer tumor growth by measuring levels of anandamide and 2-arachidonoyl glycerol as well as protein levels of CB1, CB2, ERα, ERβ, GPER, TNFα, IL-1β and IL-6 in ovarian and tumor tissues. Our results demonstrate a significant increase in ectopic ovarian tumor growth following chronic administration of JWH-133. Ovarian cancer tumor tissues chronically (30 days) treated with JWH-133 in comparison to vehicle treated groups showed an increase in endocannabinoid (AEA and 2-AG) and protein (CB2 and TNFα) levels with a decrease in GPER protein levels. Interestingly, our study emphasizes the importance of studying the impact of cannabinoid compounds on already established tumors to improve our understanding of cannabinoid-based therapies and, therefore better address clinical needs in cancer patients.https://www.frontiersin.org/articles/10.3389/fphar.2022.823132/fullovarian cancerCB2 cannabinoid agonisttumor growthanandamideJWH-1332-arachidnoylglycerol |
| spellingShingle | Henry L. Blanton Melissa C. McHann Haley De Selle Canice Lei Dancel Jose-Luis Redondo Deborah Molehin Nadezhda A. German Scott Trasti Kevin Pruitt Isabel Castro-Piedras Josée Guindon Josée Guindon Chronic Administration of Cannabinoid Receptor 2 Agonist (JWH-133) Increases Ectopic Ovarian Tumor Growth and Endocannabinoids (Anandamide and 2-Arachidonoyl Glycerol) Levels in Immunocompromised SCID Female Mice Frontiers in Pharmacology ovarian cancer CB2 cannabinoid agonist tumor growth anandamide JWH-133 2-arachidnoylglycerol |
| title | Chronic Administration of Cannabinoid Receptor 2 Agonist (JWH-133) Increases Ectopic Ovarian Tumor Growth and Endocannabinoids (Anandamide and 2-Arachidonoyl Glycerol) Levels in Immunocompromised SCID Female Mice |
| title_full | Chronic Administration of Cannabinoid Receptor 2 Agonist (JWH-133) Increases Ectopic Ovarian Tumor Growth and Endocannabinoids (Anandamide and 2-Arachidonoyl Glycerol) Levels in Immunocompromised SCID Female Mice |
| title_fullStr | Chronic Administration of Cannabinoid Receptor 2 Agonist (JWH-133) Increases Ectopic Ovarian Tumor Growth and Endocannabinoids (Anandamide and 2-Arachidonoyl Glycerol) Levels in Immunocompromised SCID Female Mice |
| title_full_unstemmed | Chronic Administration of Cannabinoid Receptor 2 Agonist (JWH-133) Increases Ectopic Ovarian Tumor Growth and Endocannabinoids (Anandamide and 2-Arachidonoyl Glycerol) Levels in Immunocompromised SCID Female Mice |
| title_short | Chronic Administration of Cannabinoid Receptor 2 Agonist (JWH-133) Increases Ectopic Ovarian Tumor Growth and Endocannabinoids (Anandamide and 2-Arachidonoyl Glycerol) Levels in Immunocompromised SCID Female Mice |
| title_sort | chronic administration of cannabinoid receptor 2 agonist jwh 133 increases ectopic ovarian tumor growth and endocannabinoids anandamide and 2 arachidonoyl glycerol levels in immunocompromised scid female mice |
| topic | ovarian cancer CB2 cannabinoid agonist tumor growth anandamide JWH-133 2-arachidnoylglycerol |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.823132/full |
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