Inhibition of C6 glioma cell proliferation by anandamide, 1-arachidonoylglycerol, and by a water soluble phosphate ester of anandamide: variability in response and involvement of arachidonic acid

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

“…Various cannabinoids, including cannabidiol, anandamide, and 2-AG, and endocannabinoid transport inhibitors have been shown to induce apoptotic cell death and to inhibit proliferation and migration in numerous murine and human tumor cell lines including glioma (C6, U87, U373, and H4), oligodendroglioma (Gos3), glioblastoma multiforme, astrocytoma (U373-MG, U87MG, and human grade IV astrocytoma), neuroblastoma (N18 TG2 and CHP100), pheochromocytoma (PC12), breast cancer (MCF-7, EFM-19, T47D, TSA-E1, and MDA-MB-231), prostate cancer (LNCaP, DU145, and PC3), colon carcinoma (SW 480), uterine cervix carcinoma (CxCa), thyroid cancer (KiMol), leukemia (CEM, HEL-92, HL60, and Jurkat cell lines), and lymphoid tumors (EL-4 and P815) tumor cells via CB 1 /CB 2 -and VR 1 receptor-dependent or independent (e.g., cyclooxygenase) mechanisms Sá nchez et al, 1998Sá nchez et al, , 2003Jacobsson et al, 2000;Maccarrone et al, 2000b;Sarker et al, 2000;McKallip et al, 2002a,b;Fowler et al, 2003;Jonsson et al, 2003;Mimeault et al, 2003;Bifulco et al, 2004;Contassot et al, 2004a,b;Hinz et al, 2004;Joseph et al, 2004;Kogan et al, 2004;Massi et al, 2004;Nithipatikom et al, 2004;Allister et al, 2005;EllertMiklaszewska et al, 2005;Herrera et al, 2005Herrera et al, , 2006Lombard et al, 2005;Powles et al, 2005;Sarfaraz et al, 2005;Vaccani et al, 2005;Carracedo et al, 2006;430 Grimaldi et al, 2006;Ligresti et al, 2006b). More importantly, systemic or local treatment with cannabinoids inhibited the growth of various types of tumor or tumor cell xenografts in vivo, including lung carcinoma (Munson et al, 1975), glioma Sá nchez et al, 2001a;Massi et al, 2004), thyroid epithelioma …”

Anti-proliferative effects of anandamide in human hepatocellular carcinoma cells

“…The antitumor effect of cannabinoids was first reported in 1975 when Δ9-THC, Δ8-THC and cannabinol were found to inhibit the growth of Lewis lung adenocarcinoma cells in vitro and in vivo, following oral administration in mice (21). Similar antitumor effects have recently been reported in a variety of cancers including breast cancer, prostate cancer, C6 glioma cells, colorectal cancer, gastric cancer and cholangiocarcinoma (7)(8)(9)(10)(11)(12)(13). In HCC, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the main active component of Cannabis sativa and JWH-015 (a cannabinoid receptor 2 (CB2)-selective agonist) were suggested to demonstrate inhibitory effects on growth both in vitro and in vivo (22).…”

“…The endogenous cannabinoid system, comprising the cannabinoid receptors CB1 and CB2 as well as enzymes regulating endocannabinoid biosynthesis and degradation, controls several physiological and pathological conditions. Recent evidence indicates that endocannabinoids influence the intracellular events controlling the proliferation and apoptosis of a number of cancer cell types, including breast cancer, prostate cancer, C6 glioma cells, colorectal cancer, gastric cancer and cholangiocarcinoma, thereby leading to antitumor effects both in vitro and in vivo (7)(8)(9)(10)(11)(12)(13). Therefore, the endocannabinoid system has been recommended as a target for the development of new drugs for cancer therapy (14).…”

Focus on the Three Key Enzymes Hydrolysing Endocannabinoids as New Drug Targets

“…Anandamide induces apoptosis in human neuroblastoma CHP100, human lymphoma U937 [19] , PC-12 cells [20], human prostatic cancer cells [21], endothelial cells [22], non-differentiated CaCo-2 cells [23], breast cancer cells [24] and C6 glioma cells. However, in this last case, it is not clear whether the effect of AEA is really due to the compound itself or to its metabolite arachidonic acid [25] (for reviews about antiproliferative effect of anandamide, see Maccarrone [26] and Parolaro [27]). AEA also plays a role in reproduction [28,29], memory processes [30][31][32][33], attenuation of cholera toxin-induced fluid accumulation [34], modulation of anxiety [35], increasing of cytochrome P450 content and activity in rat [36], modulation of epilepsy [37] and modulation of feeding [38,39].…”