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Cannabis -vs- Kidney Cancer

https://www.ncbi.nlm.nih.gov/pubmed/29792186:  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 (CB1 and CB2), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB 1 and CB 2 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 CB1 and CB2 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.

The CB1 and CB2 genes expression was shown by real-time PCR and flow cytometric and western blot analysis indicating a higher level of CB2 receptor as compared to CB1 in RCC cells. Immunocytochemical staining also confirmed the expression of the CB1 and CB2 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 CB2 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.

This study elucidated the involvement of CB2 in the in vitro inhibition of RCC cells, and future applications of CB2 agonists in the prevention and management of RCC are discussed.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434502:   Cannabinoids are a class of over 60 compounds derived from the plant cannabis sativa, as well as the synthetic or endogenous versions of these compounds.1 The primary psychoactive component of the cannabis plant — Δ9tetrahydrocannabinol, or THC — stimulates neural cannabinoid receptors, mimicking the action of endogenous cannabanoids (termed endocannabinoids).2 Endocannabinoids exert important pharmacological and physiological actions by activating CB1 (brain type receptors) and CB2 (spleen type) receptors in mammals.3 They mimic many of the effects of THC and activate both CB1 and CB2.4 The endocannabinoid system (ECS) is widely distributed in mammalian tissues and regulates nervous, cardiovascular, digestive, reproductive, immune, and metabolic functions.3

Recent studies suggest that cannabinoids contribute to maintaining balance in cell proliferation and that targeting the ECS can affect growth of several different types of cancer, including gliomas, breast, colon, prostate, and hepatocellular carcinoma.1,5–7 To date, there has only been one clinical trial looking at the antitumoural activity of cannabinoids on terminal human patients harbouring actively growing recurrent gliomas.8 Hence, this review will outline the current evidence on the antiproliferative effects of endocannabinoids in the male genitourinary malignancies, including renal, prostate, bladder, and testicular cancers, and look to explore the possible role of future human clinical trials in the field.

A limited number of studies have assessed the presence cannabinoid receptors (CB1 and CB2) in renal neoplasms and even fewer have assessed the role, if any, of the ECS in carcinogenesis and cell proliferation of renal neoplasms. To date, Larrinaga et al demonstrated that renal tumour tissues expressed mRNA of CB1 receptor in the tubular system of adult kidneys.9 Studies exploring the role of ECS in colorectal cancer have suggested that CB1 receptor loss can potentially enhance the proliferation ability of tumour cells due to lack of antitumoural effect of endocannabinoids.10 Subsequently, Larrinaga et al went on hypothesize that since CB1 is highly expressed in proximal convoluted tubules of the nephron, a similar concept may apply to renal neoplasms, where CB1 down-regulation may play a role in increased proliferation renal tumours, specifically clear-cell renal cell carcinomas.11 However, further research is needed to clarify the exact role and particular mechanisms exploring the ligands and receptors involved behind such a phenomenon.

Interestingly, another study exploring the activity of CB1 receptors in chromophobe and renal oncocytoma tissue lines found that they were expressed in similar levels to that of non-tumour tissues.3 Often times it is difficult to histologically distinguish clear-cell renal cell carcinoma from chromophobe renal cell carcinoma and having the difference in the levels of CB1 receptor, i.e., down-regulated in clear-cell renal cell carcinoma while maintaining normal levels in chromophobe, could serve as an important diagnostic tool to differentiate between the two.12

Overall, the above studies have shown the presence of CB1 receptors in clear-cell renal cell carcinoma and chromophobe renal cell carcinoma, and in vitro experiments also point to the possible role of down-regulation of CB1 receptors in promoting clear-cell renal neoplasm cell proliferation. The receptors could not only play an important role in investigating treatment options, but could also be used for diagnostic purposes.

https://www.ncbi.nlm.nih.gov/pubmed/28993942: Renal cell carcinoma (RCC) is the most common malignancy of urogenital system, and patients with RCC may face a poor prognosis. However, limited curable therapeutic options are currently available. The aim of this study is to investigate the role of Cannabinoid receptor 2 (CB2) in RCC progression.

We observed that CB2 was up-regulated in RCC tissues, and presented as an independent prognostic factor for overall survival of RCC patients and higher CB2 expression tends to have poor clinical outcomes in survival analyses. Moreover, we also observed that CB2, incorporated with pN stage, pathological grade, and recurrence or distant metastasis after surgery, could obviously enhance their prognostic accuracy in a predictive nomogram analysis. In addition, knockdown or inhibition by AM630 for the expression of CB2 in vitro could significantly decreased cell proliferation and migration, and obviously induced cell cycle arrest in G2/M of RCC cells.

CB2 expression is functionally related to cellular proliferation, migration, and cell cycle of RCC cells. Our data suggest that CB2 might be a potential therapeutic target for RCC.

https://www.ncbi.nlm.nih.gov/pubmed/28515817:  The palliative effects of cannabis sativa (marijuana), which include appetite stimulation, attenuation of nausea and emesis, and pain relief, are well known. The active components of cannabis sativa (cannabinoids) and their derivatives have received growing interest due to their diverse pharmacological activities, such as cell growth inhibition and tumour regression. The aim of this review is to look at the current evidence on the antiproliferative effects of cannabinoids in urological malignancies, including renal, prostate, bladder, and testicular cancers.

These results demonstrate that the role of endocannabinoids for urological malignancies is an area of active research. Further research is required not only to evaluate the crosstalk between cancer signaling pathways and cannabinoids, but also large randomized clinical studies with urological patients need to be conducted before cannabinoids can be introduced as potential therapeutic options for urological neoplasms.