Cannabis -vs- Melanoma

​​​​​​cannabis data.org

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005548:  One study targeted the cannabinoid receptors in order to treat melanoma in a mouse model (Blazquez et al. 2006). They showed that melanoma cells express CB1 and CB2 receptors, and that receptor activation by THC and WIN-55,212-2 led to melanoma cell-growth inhibition both in vitro and in vivo. Furthermore, they demonstrated that THC and WIN-55,212-2 caused cell cycle arrest in melanoma cells via inhibition of Akt and hypophosphorylation of the tumor suppressor protein, retinoblastoma (Rb).


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791148: If cannabinoids are postulated to have a potential anticancer effect working through the cb1 receptor, it would follow that the brain—where the cb1 receptor is the most densely populated seven-transmembrane domain G protein–coupled receptor—would be a good place to start the investigation. And, in fact, numerous studies in vitro and in animal models have suggested that cannabinoids can inhibit gliomas42. Other tumour cell lines are also inhibited by cannabinoids in vitro, and cannabinoid administration to nude mice curbs the growth of various tumour xenografts representing multiple solid and hematologic malignancies, including adenocarcinomas of the lung, breast, colon, and pancreas, and also myeloma, lymphoma, and melanoma.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171598:  Melanoma is the mainly cause of skin cancer–related deaths worldwide. CB1 and CB2 receptors are expressed in normal skin and skin tumors of mice and humans [85]. Activation of CB1/CB2 receptors induced the apoptotic death of tumorigenic epidermal cells, without affecting the nontransformed epidermal cells. WIN-55,212-2 or JWH-133 induced anti-proliferative effect in epidermal cell lines (PDV.C57 and HaCa4) and reduces malignant tumors in nude mice [85]. WIN-55,212-2 or JWH-133 induced G1 cell cycle arrest on melanoma cells, via inhibition of p-Akt and hypophosphorylation of the pRb retinoblastoma protein tumor suppressor [85].


https://www.ncbi.nlm.nih.gov/pubmed/17065222 Melanoma causes the greatest number of skin cancer-related deaths worldwide. Despite intensive research, prevention and early detection are the only effective measures against melanoma, so new therapeutic strategies are necessary for the management of this devastating disease. Here, we evaluated the efficacy of cannabinoid receptor agonists, a new family of potential antitumoral compounds, at skin melanoma. Human melanomas and melanoma cell lines express CB1 and CB2 cannabinoid receptors. Activation of these receptors decreased growth, proliferation, angiogenesis and metastasis, and increased apoptosis, of melanomas in mice. Cannabinoid antimelanoma activity was independent of the immune status of the animal, could be achieved without overt psychoactive effects and was selective for melanoma cells vs. normal melanocytes. Cannabinoid antiproliferative action on melanoma cells was due, at least in part, to cell cycle arrest at the G1-S transition via inhibition of the prosurvival protein Akt and hypophosphorylation of the pRb retinoblastoma protein tumor suppressor. These findings may contribute to the design of new chemotherapeutic strategies for the management of melanoma.


https://www.ncbi.nlm.nih.gov/pubmed/24815068During parenchymal brain metastasis formation tumor cells need to migrate through cerebral endothelial cells, which form the morphological basis of the blood-brain barrier (BBB). The mechanisms of extravasation of tumor cells are highly uncharacterized, but in some aspects recapitulate the diapedesis of leukocytes. Extravasation of leukocytes through the BBB is decreased by the activation of type 2 cannabinoid receptors (CB2); therefore, in the present study we sought to investigate the role of CB2 receptors in the interaction of melanoma cells with the brain endothelium. First, we identified the presence of CB1, CB2(A), GPR18 (transcriptional variant 1) and GPR55 receptors in brain endothelial cells, while melanoma cells expressed CB1, CB2(A), GPR18 (transcriptional variants 1 and 2), GPR55 and GPR119. We observed that activation of CB2 receptors with JWH-133 reduced the adhesion of melanoma cells to the layer of brain endothelial cells. JWH-133 decreased the transendothelial migration rate of melanoma cells as well. Our results suggest that changes induced in endothelial cells are critical in the mediation of the effect of CB2 agonists. Our data identify CB2 as a potential target in reducing the number of brain metastastes originating from melanoma.