The Endocannabinoid, Anandamide, Acts as a Novel Inhibitor of LPS-Induced Inflammasome Activation in Human Gastric Cancer AGS Cell Line: Involvement of CB1 and TRPV1 Receptors
Inflammasome activation is a pivotal step for the maturation of IL-1β, which is involved in the development and progression of gastric cancer (GC). Endocannabinoids, such as anandamide (AEA), are emerging as new anticancer therapeutic agents; however, their effects on inflammasome components and und...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/6698049 |
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| author | Sahar Sadat Sedeighzadeh Hamid Galehdari Mohammad Reza Tabandeh Mehdi Shamsara Ali Roohbakhsh |
| author_facet | Sahar Sadat Sedeighzadeh Hamid Galehdari Mohammad Reza Tabandeh Mehdi Shamsara Ali Roohbakhsh |
| author_sort | Sahar Sadat Sedeighzadeh |
| collection | DOAJ |
| description | Inflammasome activation is a pivotal step for the maturation of IL-1β, which is involved in the development and progression of gastric cancer (GC). Endocannabinoids, such as anandamide (AEA), are emerging as new anticancer therapeutic agents; however, their effects on inflammasome components and underlying mechanisms have not been well elucidated. This study was designed to investigate the effects of AEA on the expression of inflammasome components in lipopolysaccharide- (LPS-) stimulated AGS cells. Moreover, we explored the involvement of cannabinoid receptors (CRs), including CB1R and TRPV1R, in the observed effects of AEA. Our results showed that inflammation was induced by LPS (10 μg/ml) in AGS cells, and inflammasome components (NLRP3, MLRC4, ASC, IL-18, and IL-1β) were overexpressed. Exposure to AEA (10 μM, 24 h) before or after inflammation induction downregulated the expression of inflammasome components and attenuated inflammasome activation as demonstrated by cleavage of caspase 1 and matured IL-1β secretion, although AEA pretreatment showed more reducing effects on the inflammasome activation. In addition, blocking of CB1R and TRPV1R by application of AM-251 and AMG-9810 antagonists remarkably reversed the observed effects of AEA and revealed that NLRP3, NLRC4, and IL-1β genes were mainly regulated via CB1R, while TRPV1R could only regulate the expression of IL-1β and IL-18 genes. In conclusion, our results would indicate a novel anticancer effect of anandamide by attenuation of inflammasome activation and consequently reducing IL-1β production in human AGS cancer cell line via CB1R and TRPV1R. |
| format | Article |
| id | doaj-art-985311b17563447a9d75d326b64a2814 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-985311b17563447a9d75d326b64a28142025-02-03T06:43:42ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/66980496698049The Endocannabinoid, Anandamide, Acts as a Novel Inhibitor of LPS-Induced Inflammasome Activation in Human Gastric Cancer AGS Cell Line: Involvement of CB1 and TRPV1 ReceptorsSahar Sadat Sedeighzadeh0Hamid Galehdari1Mohammad Reza Tabandeh2Mehdi Shamsara3Ali Roohbakhsh4Department of Biological Sciences, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz 61357-831351, IranDepartment of Biological Sciences, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz 61357-831351, IranStem Cells and Transgenic Technology Research Center, Shahid Chamran University of Ahvaz, Ahvaz 61357-831351, IranDepartment of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran 14155-6343, IranDepartment of Pharmacodynamics and Toxicology, Mashhad University of Medical Sciences, Mashhad 91388-13944, IranInflammasome activation is a pivotal step for the maturation of IL-1β, which is involved in the development and progression of gastric cancer (GC). Endocannabinoids, such as anandamide (AEA), are emerging as new anticancer therapeutic agents; however, their effects on inflammasome components and underlying mechanisms have not been well elucidated. This study was designed to investigate the effects of AEA on the expression of inflammasome components in lipopolysaccharide- (LPS-) stimulated AGS cells. Moreover, we explored the involvement of cannabinoid receptors (CRs), including CB1R and TRPV1R, in the observed effects of AEA. Our results showed that inflammation was induced by LPS (10 μg/ml) in AGS cells, and inflammasome components (NLRP3, MLRC4, ASC, IL-18, and IL-1β) were overexpressed. Exposure to AEA (10 μM, 24 h) before or after inflammation induction downregulated the expression of inflammasome components and attenuated inflammasome activation as demonstrated by cleavage of caspase 1 and matured IL-1β secretion, although AEA pretreatment showed more reducing effects on the inflammasome activation. In addition, blocking of CB1R and TRPV1R by application of AM-251 and AMG-9810 antagonists remarkably reversed the observed effects of AEA and revealed that NLRP3, NLRC4, and IL-1β genes were mainly regulated via CB1R, while TRPV1R could only regulate the expression of IL-1β and IL-18 genes. In conclusion, our results would indicate a novel anticancer effect of anandamide by attenuation of inflammasome activation and consequently reducing IL-1β production in human AGS cancer cell line via CB1R and TRPV1R.http://dx.doi.org/10.1155/2021/6698049 |
| spellingShingle | Sahar Sadat Sedeighzadeh Hamid Galehdari Mohammad Reza Tabandeh Mehdi Shamsara Ali Roohbakhsh The Endocannabinoid, Anandamide, Acts as a Novel Inhibitor of LPS-Induced Inflammasome Activation in Human Gastric Cancer AGS Cell Line: Involvement of CB1 and TRPV1 Receptors Mediators of Inflammation |
| title | The Endocannabinoid, Anandamide, Acts as a Novel Inhibitor of LPS-Induced Inflammasome Activation in Human Gastric Cancer AGS Cell Line: Involvement of CB1 and TRPV1 Receptors |
| title_full | The Endocannabinoid, Anandamide, Acts as a Novel Inhibitor of LPS-Induced Inflammasome Activation in Human Gastric Cancer AGS Cell Line: Involvement of CB1 and TRPV1 Receptors |
| title_fullStr | The Endocannabinoid, Anandamide, Acts as a Novel Inhibitor of LPS-Induced Inflammasome Activation in Human Gastric Cancer AGS Cell Line: Involvement of CB1 and TRPV1 Receptors |
| title_full_unstemmed | The Endocannabinoid, Anandamide, Acts as a Novel Inhibitor of LPS-Induced Inflammasome Activation in Human Gastric Cancer AGS Cell Line: Involvement of CB1 and TRPV1 Receptors |
| title_short | The Endocannabinoid, Anandamide, Acts as a Novel Inhibitor of LPS-Induced Inflammasome Activation in Human Gastric Cancer AGS Cell Line: Involvement of CB1 and TRPV1 Receptors |
| title_sort | endocannabinoid anandamide acts as a novel inhibitor of lps induced inflammasome activation in human gastric cancer ags cell line involvement of cb1 and trpv1 receptors |
| url | http://dx.doi.org/10.1155/2021/6698049 |
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