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Cannabis -vs- Non-Hodgkin's Lymphoma

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171598/ CB1 and CB2 receptors were over-expressed in mantle cell lymphoma (MCL), and B cell non-Hodgkin lymphoma [114-115]. Δ9-THC inhibits cell viability and increased apoptosis both in vitro in EL4 and MCL cells and EL4 tumor bearing mice. In next studies the combination of Δ9-THC and other cytotoxic agents induced apoptosis in leukemia cells by MAPK/ERK pathway [114, 116]. In addition R(+)-methanandamide and WIN-55,212-2 induced apoptosis in MCL cells, was associated with ceramide accumulation and p38, depolarization of the mitochondrial membrane, and caspase activation [117]. R(+)-methanandamide also induced apoptosis in CLL cells [118]. In contrast, cannabinoids decreased cell viability as assessed by metabolic activity. The persistent expression of mammalian homolog of Atg8 with microtubule-associated protein-1 light chain-3 II (LC3 II) and p62, as well as the lack of protection from chloroquine, indicates that lysosomal degradation is not involved in this cytoplasmic vacuolation process, distinguishing from classical autophagy [119]. Paraptosis-like cell death-a third type of a programmed cell death occurred in response to cannabinoids [119].



http://onlinelibrary.wiley.com/doi/10.1002/ijc.23584Endogenous and synthetic cannabinoids exert antiproliferative and proapoptotic effects in various types of cancer and in mantle cell lymphoma (MCL). In this study, we evaluated the expression of cannabinoid receptors type 1 and type 2 (CB1 and CB2) in non-Hodgkin lymphomas of B cell type (n = 62). A majority of the lymphomas expressed higher mRNA levels of CB1 and/or CB2 as compared to reactive lymphoid tissue. With the exception of MCL, which uniformly overexpresses both CB1 and CB2, the levels of cannabinoid receptors within other lymphoma entities were highly variable, ranging from 0.1 to 224 times the expression in reactive lymph nodes. Low levels of the splice variant CB1a, previously shown to have a different affinity for cannabinoids than CB1, were detected in 44% of the lymphomas, while CB1b expression was not detected. In functional studies using MCL, Burkitt lymphoma (BL), chronic lymphatic leukemia (CLL) and plasma cell leukemia cell lines, the stable anandamide analog R(+)-methanandamide (R(+)-MA) induced cell death only in MCL and CLL cells, which overexpressed both cannabinoid receptors, but not in BL. In vivo treatment with R(+)-MA caused a significant reduction of tumor size and mitotic index in mice xenografted with human MCL. Together, our results suggest that therapies using cannabinoid receptor ligands will have efficiency in reducing tumor burden in malignant lymphoma overexpressing CB1 and CB2. © 2008 Wiley-Liss, Inc.


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366283/
Endocannabinoids are bioactive lipids that have a range of interesting activities mediated by two G-protein-coupled receptors (CB1 and CB2) and other putative targets [1-3]. The CB1 receptor is present in the central nervous system and mediates the psychotropic effects of exogenous cannabinoids such as Δ9-tetrahydrocannabinol (THC), the active component of marijuana. In the brain, endocannabinoids and cannabinoids combine with CB1 cannabinoid receptors on axon terminals and regulate ion channel activity and neurotransmitter release [4]. Binding to the CB1 receptor is responsible for the analgesic activity of endocannabinoids as well as many other effects including locomotion and temperature control [5]. The CB2 receptor is present in inflammatory tissues and mediates the anti-inflammatory effects of endocannabinoids and plant-derived cannabinols [6]. Both the CB1 and CB2 receptors couple to Gi and reduce intracellular cAMP levels.

The association of CB receptor expression with tumor malignancy and disease outcome in cancer has been studied in several settings. These studies suggest that the role of CB1 and CB2 receptor expression in relation to disease prognosis and outcome is dependent on the specific cancer type. Analyses of astrocytomas demonstrate that 70% of the tumors express CB1 and/or CB2 and the extent of CB2 expression correlates with tumor malignancy [41]. In gliomas, a higher expression of CB2 compared to CB1 has been reported and is related to tumor grade [41]. In addition to tumors, tumor-associated endothelial cells exhibit immunoreactivity for CB receptors similar to that observed in tumor cells [42]. Increased expression of CB1 has been reported in mantle cell lymphoma and of both CB1 and CB2 in non-Hodgkin lymphoma as compared to reactive lymph nodes [43, 44]. In contrast, a greatly reduced expression of CB1, but not CB2, was found in colon carcinoma compared with adjacent normal mucosa [19].