Back to Search
Start Over
Involvement of the CB 2 cannabinoid receptor in cell growth inhibition and G0/G1 cell cycle arrest via the cannabinoid agonist WIN 55,212-2 in renal cell carcinoma.
- Source :
-
BMC cancer [BMC Cancer] 2018 May 23; Vol. 18 (1), pp. 583. Date of Electronic Publication: 2018 May 23. - Publication Year :
- 2018
-
Abstract
- Background: The anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. Many of these anti-tumor effects are mediated via cannabinoid receptor types 1 and 2 (CB <subscript>1</subscript> and CB <subscript>2</subscript> ), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB <subscript>1</subscript> and CB <subscript>2</subscript> receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. In view of their further use for potential treatments, we thus investigated the roles of CB <subscript>1</subscript> and CB <subscript>2</subscript> receptors in the anti-proliferative action and signal transduction triggered by synthetic cannabinoid agonists [such as JWH-133 and WIN 55,212-2 (WIN-55)] in RCC cell lines.<br />Methods: Human RCC cell lines were used for this study. The CB <subscript>1</subscript> and CB <subscript>2</subscript> gene expression levels were analyzed using real-time PCR. Flow cytometric, immunocytochemical and western blot analyses were performed to confirm CB <subscript>1</subscript> and CB <subscript>2</subscript> receptor protein expression. The anti-proliferative effects of synthetic cannabinoids were investigated on cell viability assay. The CB <subscript>1</subscript> and CB <subscript>2</subscript> receptors were blocked pharmacologically with the antagonists SR141716A and AM-630, respectively, to investigate the effects of the agonists JWH-133 and WIN-55. Cell cycle, apoptosis and LDH-based cytotoxicity were analyzed on cannabinoid-treated RCC cells.<br />Results: The CB1 and CB2 genes expression was shown by real-time PCR and flow cytometric and western blot analysis indicating a higher level of CB <subscript>2</subscript> receptor as compared to CB <subscript>1</subscript> in RCC cells. Immunocytochemical staining also confirmed the expression of the CB <subscript>1</subscript> and CB <subscript>2</subscript> proteins. We also found that the synthetic cannabinoid agonist WIN-55 exerted anti-proliferative and cytotoxic effects by inhibiting the growth of RCC cell lines, while the CB <subscript>2</subscript> agonist JWH-133 did not. Pharmacologically blocking the CB1 and CB2 receptors with their respective antagonists SR141716A and AM-630, followed by the WIN-55 treatment of RCC cells allowed uncovering the involvement of CB2, which led to an arrest in the G0/G1 phase of the cell cycle and apoptosis.<br />Conclusions: This study elucidated the involvement of CB <subscript>2</subscript> in the in vitro inhibition of RCC cells, and future applications of CB <subscript>2</subscript> agonists in the prevention and management of RCC are discussed.
- Subjects :
- Apoptosis drug effects
Benzoxazines therapeutic use
Cannabinoid Receptor Agonists therapeutic use
Cannabinoid Receptor Antagonists pharmacology
Carcinoma, Renal Cell pathology
Cell Line, Tumor
Cell Proliferation drug effects
Drug Screening Assays, Antitumor
G1 Phase Cell Cycle Checkpoints drug effects
Humans
Kidney Neoplasms pathology
Morpholines therapeutic use
Naphthalenes therapeutic use
Receptor, Cannabinoid, CB1 agonists
Receptor, Cannabinoid, CB1 antagonists & inhibitors
Receptor, Cannabinoid, CB1 metabolism
Receptor, Cannabinoid, CB2 agonists
Receptor, Cannabinoid, CB2 antagonists & inhibitors
Signal Transduction drug effects
Benzoxazines pharmacology
Cannabinoid Receptor Agonists pharmacology
Carcinoma, Renal Cell drug therapy
Kidney Neoplasms drug therapy
Morpholines pharmacology
Naphthalenes pharmacology
Receptor, Cannabinoid, CB2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2407
- Volume :
- 18
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC cancer
- Publication Type :
- Academic Journal
- Accession number :
- 29792186
- Full Text :
- https://doi.org/10.1186/s12885-018-4496-1