Cannabis -vs- Kidney Cancer  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.   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.