{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:25:33Z","timestamp":1791318333094,"version":"4.3.1"},"reference-count":180,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T00:00:00Z","timestamp":1636934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Despite the long history of cannabinoid use for medicinal and ritual purposes, an endogenous system of cannabinoid-controlled receptors, as well as their ligands and the enzymes that synthesise and degrade them, was only discovered in the 1990s. Since then, the endocannabinoid system has attracted widespread scientific interest regarding new pharmacological targets in cancer treatment among other reasons. Meanwhile, extensive preclinical studies have shown that cannabinoids have an inhibitory effect on tumour cell proliferation, tumour invasion, metastasis, angiogenesis, chemoresistance and epithelial-mesenchymal transition (EMT) and induce tumour cell apoptosis and autophagy as well as immune response. Appropriate cannabinoid compounds could moreover be useful for cancer patients as potential combination partners with other chemotherapeutic agents to increase their efficacy while reducing unwanted side effects. In addition to the direct activation of cannabinoid receptors through the exogenous application of corresponding agonists, another strategy is to activate these receptors by increasing the endocannabinoid levels at the corresponding pathological hotspots. Indeed, a number of studies accordingly showed an inhibitory effect of blockers of the endocannabinoid-degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) on tumour development and spread. This review summarises the relevant preclinical studies with FAAH and MAGL inhibitors compared to studies with cannabinoids and provides an overview of the regulation of the endocannabinoid system in cancer.<\/jats:p>","DOI":"10.3390\/cancers13225701","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T08:19:20Z","timestamp":1636964360000},"page":"5701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["The Endocannabinoid System as a Pharmacological Target for New Cancer Therapies"],"prefix":"10.3390","volume":"13","author":[{"given":"Robert","family":"Ramer","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Rostock University Medical Centre, Schillingallee 70, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Wittig","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Rostock University Medical Centre, Schillingallee 70, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Hinz","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Rostock University Medical Centre, Schillingallee 70, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1126\/science.1470919","article-title":"Isolation and structure of a brain constituent that binds to the cannabinoid receptor","volume":"258","author":"Hanus","year":"1992","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0006-2952(95)00109-D","article-title":"Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors","volume":"50","author":"Mechoulam","year":"1995","journal-title":"Biochem. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1073\/pnas.061029898","article-title":"2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor","volume":"98","author":"Hanus","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1042\/bj3510817","article-title":"N-acyl-dopamines: Novel synthetic CB1 cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo","volume":"351","author":"Bisogno","year":"2000","journal-title":"Biochem. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1124\/jpet.301.3.1020","article-title":"Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor","volume":"301","author":"Porter","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/346561a0","article-title":"Structure of a cannabinoid receptor and functional expression of the cloned cDNA","volume":"346","author":"Matsuda","year":"1990","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/365061a0","article-title":"Molecular characterization of a peripheral receptor for cannabinoids","volume":"365","author":"Munro","year":"1993","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/sj.bjp.0707442","article-title":"The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: \u03949-tetrahydrocannabinol, cannabidiol and \u03949-tetrahydrocannabivarin","volume":"153","author":"Pertwee","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/22761","article-title":"Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide","volume":"400","author":"Zygmunt","year":"1999","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/sj.bjp.0704327","article-title":"Molecular targets for cannabidiol and its synthetic analogues: Effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide","volume":"134","author":"Bisogno","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0169-328X(98)00277-0","article-title":"Identification and cloning of three novel human G protein-coupled receptor genes GPR52, \u03a8GPR53 and GPR55: GPR55 is extensively expressed in human brain","volume":"64","author":"Sawzdargo","year":"1999","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1038\/sj.bjp.0707460","article-title":"The orphan receptor GPR55 is a novel cannabinoid receptor","volume":"152","author":"Ryberg","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.bbalip.2008.01.006","article-title":"Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine","volume":"1781","author":"Artmann","year":"2008","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1080\/03602532.2018.1428344","article-title":"Targeting the endocannabinoid system as a potential anticancer approach","volume":"50","author":"Schwarz","year":"2018","journal-title":"Drug Metab. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.phrs.2009.02.010","article-title":"The endocannabinoid system: Its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploitation","volume":"60","year":"2009","journal-title":"Pharmacol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/0006-2952(93)90486-G","article-title":"Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist","volume":"46","author":"Deutsch","year":"1993","journal-title":"Biochem. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.chembiol.2007.11.006","article-title":"A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol","volume":"14","author":"Blankman","year":"2007","journal-title":"Chem. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cell.2009.11.027","article-title":"Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis","volume":"140","author":"Nomura","year":"2010","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"22937","DOI":"10.1016\/S0021-9258(17)31599-5","article-title":"Inhibitors of arachidonoyl ethanolamide hydrolysis","volume":"269","author":"Koutek","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5935","DOI":"10.1021\/bi00074a003","article-title":"Slow- and tight-binding inhibitors of the 85-kDa human phospholipase A2","volume":"32","author":"Street","year":"1993","journal-title":"Biochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1006\/bbrc.1998.8874","article-title":"Arachidonoylserotonin and other novel inhibitors of fatty acid amide hydrolase","volume":"248","author":"Bisogno","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/nm803","article-title":"Modulation of anxiety through blockade of anandamide hydrolysis","volume":"9","author":"Kathuria","year":"2003","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1038\/nature03658","article-title":"An endocannabinoid mechanism for stress-induced analgesia","volume":"435","author":"Hohmann","year":"2005","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/sj.bjp.0706971","article-title":"Lack of selectivity of URB602 for 2-oleoylglycerol compared to anandamide hydrolysis in vitro","volume":"150","author":"Vandevoorde","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.chembiol.2009.05.009","article-title":"Characterization of monoacylglycerol lipase inhibition reveals differences in central and peripheral endocannabinoid metabolism","volume":"16","author":"Long","year":"2009","journal-title":"Chem. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1021\/cn400116z","article-title":"Evaluation of NHS carbamates as a potent and selective class of endocannabinoid hydrolase inhibitors","volume":"4","author":"Niphakis","year":"2013","journal-title":"ACS Chem. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1021\/cb400261h","article-title":"Proteome-wide reactivity profiling identifies diverse carbamate chemotypes tuned for serine hydrolase inhibition","volume":"8","author":"Chang","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9062","DOI":"10.1021\/acs.jmedchem.8b00951","article-title":"Identification of ABX-1431, a Selective Inhibitor of Monoacylglycerol Lipase and Clinical Candidate for Treatment of Neurological Disorders","volume":"61","author":"Cisar","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_29","unstructured":"U.S. National Library of Medicine (2021, October 20). ClinicalTrials.gov, Available online: https:\/\/www.clinicaltrials.gov\/ct2\/results?recrs=&cond=&term=ABX-1431&cntry=&state=&city=&dist=."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/s41589-019-0243-4","article-title":"Pharmacological convergence reveals a lipid pathway that regulates C. elegans lifespan","volume":"15","author":"Chen","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.18632\/oncoscience.289","article-title":"The potential relevance of the endocannabinoid, 2-arachidonoylglycerol, in diffuse large B-cell lymphoma","volume":"3","author":"Zhang","year":"2016","journal-title":"Oncoscience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1210\/en.2009-0883","article-title":"The levels of the endocannabinoid receptor CB2 and its ligand 2-arachidonoylglycerol are elevated in endometrial carcinoma","volume":"151","author":"Guida","year":"2010","journal-title":"Endocrinology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"447","DOI":"10.3892\/or.2015.3973","article-title":"Endocannabinoid and ceramide levels are altered in patients with colorectal cancer","volume":"34","author":"Chen","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1111\/j.1471-4159.2011.07625.x","article-title":"Alteration of endocannabinoid system in human gliomas","volume":"120","author":"Wu","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1046\/j.1471-4159.2001.00092.x","article-title":"Gas chromatography-mass spectrometry analysis of endogenous cannabinoids in healthy and tumoral human brain and human cells in culture","volume":"76","author":"Maccarrone","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1182\/blood-2003-12-4357","article-title":"The peripheral cannabinoid receptor Cb2, frequently expressed on AML blasts, either induces a neutrophilic differentiation block or confers abnormal migration properties in a ligand-dependent manner","volume":"104","author":"Rayman","year":"2004","journal-title":"Blood"},{"key":"ref_37","first-page":"5784","article-title":"Inhibition of glioma growth in vivo by selective activation of the CB2 cannabinoid receptor","volume":"61","author":"Rueda","year":"2001","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1111\/j.1471-4159.2006.03911.x","article-title":"Cannabinoid receptors in human astroglial tumors","volume":"98","author":"Sahan","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.neuint.2010.03.007","article-title":"Opposite changes in cannabinoid CB1 and CB2 receptor expression in human gliomas","volume":"56","author":"Hostalot","year":"2010","journal-title":"Neurochem. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1007\/s00381-016-3243-7","article-title":"Spontaneous involution of pediatric low-grade gliomas: High expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system","volume":"32","author":"Sredni","year":"2016","journal-title":"Childs Nerv. Syst."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ellert-Miklaszewska, A., Ciechomska, I.A., and Kaminska, B. (2021). Synthetic Cannabinoids Induce Autophagy and Mitochondrial Apoptotic Pathways in Human Glioblastoma Cells Independently of Deficiency in TP53 or PTEN Tumor Suppressors. Cancers, 13.","DOI":"10.3390\/cancers13030419"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6615","DOI":"10.1158\/0008-5472.CAN-05-4566","article-title":"\u03949-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation","volume":"66","author":"Caffarel","year":"2006","journal-title":"Cancer Res."},{"key":"ref_43","first-page":"1327","article-title":"Identification of genes with altered expression in medullary breast cancer vs. ductal breast cancer and normal breast epithelia","volume":"28","author":"Gjerstorff","year":"2006","journal-title":"Int. J. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Nasser, M.W., Qamri, Z., Deol, Y.S., Smith, D., Shilo, K., Zou, X., and Ganju, R.K. (2011). Crosstalk between chemokine receptor CXCR4 and cannabinoid receptor CB2 in modulating breast cancer growth and invasion. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023901"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Shubbar, E., Helou, K., Kov\u00e1cs, A., Nemes, S., Hajizadeh, S., Enerb\u00e4ck, C., and Einbeigi, Z. (2013). High levels of \u03b3-glutamyl hydrolase (GGH) are associated with poor prognosis and unfavorable clinical outcomes in invasive breast cancer. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-47"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/onc.2012.34","article-title":"Potential tumor-suppressive role of monoglyceride lipase in human colorectal cancer","volume":"32","author":"Sun","year":"2013","journal-title":"Oncogene"},{"key":"ref_47","first-page":"djv077","article-title":"Role of cannabinoid receptor CB2 in HER2 pro-oncogenic signaling in breast cancer","volume":"107","author":"Andradas","year":"2015","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1073\/pnas.1815034116","article-title":"Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer","volume":"116","author":"Moreno","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"377","DOI":"10.21873\/cgp.20143","article-title":"Comparative Proteome Analysis of Breast Cancer Tissues Highlights the Importance of Glycerol-3-phosphate Dehydrogenase 1 and Monoacylglycerol Lipase in Breast Cancer Metabolism","volume":"16","author":"Yoneten","year":"2019","journal-title":"Cancer Genom. Proteom."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/S0016-5085(03)00881-3","article-title":"Possible endocannabinoid control of colorectal cancer growth","volume":"125","author":"Ligresti","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7691","DOI":"10.1158\/1078-0432.CCR-08-0799","article-title":"Cannabinoid receptor activation induces apoptosis through tumor necrosis factor \u03b1-mediated ceramide de novo synthesis in colon cancer cells","volume":"14","author":"Cianchi","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6468","DOI":"10.1158\/0008-5472.CAN-08-0896","article-title":"Loss of cannabinoid receptor 1 accelerates intestinal tumor growth","volume":"68","author":"Wang","year":"2008","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.canlet.2011.03.007","article-title":"Monoacylglycerol lipase (MAGL) knockdown inhibits tumor cells growth in colorectal cancer","volume":"307","author":"Ye","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"870","DOI":"10.3892\/ol.2012.1081","article-title":"Expression of the cannabinoid type I receptor and prognosis following surgery in colorectal cancer","volume":"5","author":"Jung","year":"2013","journal-title":"Oncol. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"131","DOI":"10.18632\/oncoscience.119","article-title":"Cannabinoids receptor type 2, CB2, expression correlates with human colon cancer progression and predicts patient survival","volume":"2","author":"Tejerina","year":"2015","journal-title":"Oncoscience"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/ijc.31030","article-title":"G protein-coupled receptor GPR55 promotes colorectal cancer and has opposing effects to cannabinoid receptor 1","volume":"142","author":"Hasenoehrl","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1038\/s41467-018-04999-8","article-title":"Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression","volume":"9","author":"Xiang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Tutino, V., Caruso, M.G., De Nunzio, V., Lorusso, D., Veronese, N., Gigante, I., Notarnicola, M., and Giannelli, G. (2019). Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer. Cancers, 11.","DOI":"10.3390\/cancers11050708"},{"key":"ref_59","first-page":"8527","article-title":"\u22069-tetrahydrocannabinol inhibits epithelial-mesenchymal transition and metastasis by targeting matrix metalloproteinase-9 in endometrial cancer","volume":"15","author":"Zhang","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"430","DOI":"10.3389\/fonc.2019.00430","article-title":"Identification of Novel Predictive Biomarkers for Endometrial Malignancies: N-Acylethanolamines","volume":"9","author":"Ayakannu","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.3389\/fonc.2019.01363","article-title":"Expression and Function of the Endocannabinoid Modulating Enzymes Fatty Acid Amide Hydrolase and N-Acylphosphatidylethanolamine-Specific Phospholipase D in Endometrial Carcinoma","volume":"9","author":"Ayakannu","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1111\/jog.14070","article-title":"Effect of monoacylglycerol lipase on the tumor growth in endometrial cancer","volume":"45","author":"Li","year":"2019","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Andradas, C., Byrne, J., Kuchibhotla, M., Ancliffe, M., Jones, A.C., Carline, B., Hii, H., Truong, A., Storer, L.C.D., and Ritzmann, T.A. (2021). Assessment of Cannabidiol and \u03949-Tetrahydrocannabiol in Mouse Models of Medulloblastoma and Ependymoma. Cancers, 13.","DOI":"10.3390\/cancers13020330"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/pin.12495","article-title":"Overexpression of cannabinoid receptor 1 in esophageal squamous cell carcinoma is correlated with metastasis to lymph nodes and distant organs, and poor prognosis","volume":"67","author":"Hijiya","year":"2017","journal-title":"Pathol. Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7503","DOI":"10.2147\/OTT.S181706","article-title":"mir-23b-3p and mir-130a-5p affect cell growth, migration and invasion by targeting CB1R via the Wnt\/\u03b2-catenin signaling pathway in gastric carcinoma","volume":"11","author":"Xian","year":"2018","journal-title":"Onco Targets Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1471-4159.2005.03013.x","article-title":"Endocannabinoid metabolism in human glioblastomas and meningiomas compared to human non-tumour brain tissue","volume":"93","author":"Petersen","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.brainresbull.2009.01.011","article-title":"Predominant CB2 receptor expression in endothelial cells of glioblastoma in humans","volume":"79","author":"Schley","year":"2009","journal-title":"Brain Res. Bull."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.bjoms.2013.03.015","article-title":"Cannabinoid receptor-2 immunoreactivity is associated with survival in squamous cell carcinoma of the head and neck","volume":"51","author":"Leusink","year":"2013","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cancergencyto.2006.06.014","article-title":"Overexpression of cannabinoid receptors CB1 and CB2 correlates with improved prognosis of patients with hepatocellular carcinoma","volume":"171","author":"Xu","year":"2006","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1002\/hep.27686","article-title":"Cannabinoid receptor 1 promotes hepatocellular carcinoma initiation and progression through multiple mechanisms","volume":"61","author":"Mukhopadhyay","year":"2015","journal-title":"Hepatology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"35784","DOI":"10.1038\/srep35784","article-title":"Monoacylglycerol Lipase: A Novel Potential Therapeutic Target and Prognostic Indicator for Hepatocellular Carcinoma","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s13045-016-0361-3","article-title":"Monoacylglycerol lipase promotes progression of hepatocellular carcinoma via NF-\u03baB-mediated epithelial-mesenchymal transition","volume":"9","author":"Zhu","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_73","first-page":"1530","article-title":"Endocannabinoid system and the expression of endogenous ceramides in human hepatocellular carcinoma","volume":"18","author":"Yang","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41419-017-0188-z","article-title":"Monoglyceride lipase gene knockout in mice leads to increased incidence of lung adenocarcinoma","volume":"9","author":"Liu","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"109080","DOI":"10.1016\/j.biopha.2019.109080","article-title":"The oncogenic role of CB2 in the progression of non-small-cell lung cancer","volume":"117","author":"Xu","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Milian, L., Mata, M., Alcacer, J., Oliver, M., Sancho-Tello, M., Mart\u00edn de Llano, J.J., Camps, C., Galbis, J., Carretero, J., and Carda, C. (2020). Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0228909"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"102696","DOI":"10.1016\/j.ebiom.2020.102696","article-title":"Enhanced monoacylglycerol lipolysis by ABHD6 promotes NSCLC pathogenesis","volume":"53","author":"Tang","year":"2020","journal-title":"eBioMedicine"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"559568","DOI":"10.3389\/fonc.2020.559568","article-title":"Monoacylglycerol Lipase Knockdown Inhibits Cell Proliferation and Metastasis in Lung Adenocarcinoma","volume":"10","author":"Zhang","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1038\/sj.leu.2403057","article-title":"High level of cannabinoid receptor 1, absence of regulator of G protein signalling 13 and differential expression of Cyclin D1 in mantle cell lymphoma","volume":"17","author":"Islam","year":"2003","journal-title":"Leukemia"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"550","DOI":"10.18632\/oncoscience.77","article-title":"Perturbations of the endocannabinoid system in mantle cell lymphoma: Correlations to clinical and pathological features","volume":"1","author":"Wasik","year":"2014","journal-title":"Oncoscience"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"549","DOI":"10.4103\/0973-1482.106534","article-title":"Cannabinoid receptor 2 is upregulated in melanoma","volume":"8","author":"Zhao","year":"2012","journal-title":"J. Cancer Res. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1111\/jdv.14455","article-title":"Expression of monoacylglycerol lipase as a marker of tumour invasion and progression in malignant melanoma","volume":"31","author":"Baba","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1007\/s13277-015-4182-8","article-title":"Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: Associations with clinicopathological parameters and patients\u2019 survival","volume":"37","author":"Theocharis","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_84","first-page":"3704","article-title":"Monoacylglycerol lipase promotes metastases in nasopharyngeal carcinoma","volume":"7","author":"Hu","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"234.e1","DOI":"10.1016\/j.ajog.2014.04.004","article-title":"Cannabinoid receptor type 1 immunoreactivity and disease severity in human epithelial ovarian tumors","volume":"211","author":"Messalli","year":"2014","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/ijc.23114","article-title":"Cannabinoids in pancreatic cancer: Correlation with survival and pain","volume":"122","author":"Michalski","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_87","first-page":"2687","article-title":"Normal human pituitary gland and pituitary adenomas express cannabinoid receptor type 1 and synthesize endogenous cannabinoids: First evidence for a direct role of cannabinoids on hormone modulation at the human pituitary level","volume":"86","author":"Pagotto","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1002\/ijc.23674","article-title":"Expression and function of fatty acid amide hydrolase in prostate cancer","volume":"123","author":"Endsley","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.ejca.2008.10.010","article-title":"A high cannabinoid CB1 receptor immunoreactivity is associated with disease severity and outcome in prostate cancer","volume":"45","author":"Chung","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00432-008-0482-3","article-title":"Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma","volume":"135","author":"Czifra","year":"2009","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Thors, L., Bergh, A., Persson, E., Hammarsten, P., Stattin, P., Egevad, L., Granfors, T., and Fowler, C.J. (2010). Fatty acid amide hydrolase in prostate cancer: Association with disease severity and outcome, CB1 receptor expression and regulation by IL-4. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012275"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.ebiom.2019.05.048","article-title":"Paradoxical effects of JZL184, an inhibitor of monoacylglycerol lipase, on bone remodelling in healthy and cancer-bearing mice","volume":"44","author":"Marino","year":"2019","journal-title":"eBioMedicine"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1369\/jhc.2010.957126","article-title":"Cannabinoid CB\u2081 receptor is downregulated in clear cell renal cell carcinoma","volume":"58","author":"Larrinaga","year":"2010","journal-title":"J. Histochem. Cytochem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.clinbiochem.2012.12.023","article-title":"Cannabinoid CB1 receptor is expressed in chromophobe renal cell carcinoma and renal oncocytoma","volume":"46","author":"Larrinaga","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00432-017-2527-y","article-title":"Cannabinoid receptor 2 as a novel target for promotion of renal cell carcinoma prognosis and progression","volume":"144","author":"Wang","year":"2018","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.exer.2011.12.002","article-title":"Altered calcium regulation by thermosensitive transient receptor potential channels in etoposide-resistant WERI-Rb1 retinoblastoma cells","volume":"94","author":"Mergler","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1158\/1535-7163.MCT-08-1147","article-title":"Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma","volume":"8","author":"Oesch","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"839403","DOI":"10.1155\/2015\/839403","article-title":"Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions","volume":"2015","author":"Lakiotaki","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"272","DOI":"10.18632\/oncoscience.33","article-title":"Regulation of circulating endocannabinoids associated with cancer and metastases in mice and humans","volume":"1","author":"Sailler","year":"2014","journal-title":"Oncoscience"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/jnci\/55.3.597","article-title":"Antineoplastic activity of cannabinoids","volume":"55","author":"Munson","year":"1975","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"8375","DOI":"10.1073\/pnas.95.14.8375","article-title":"The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation","volume":"95","author":"Melck","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1080\/14728222.2016.1177512","article-title":"Antitumorigenic targets of cannabinoids\u2014Current status and implications","volume":"20","author":"Ramer","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/73171","article-title":"Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation","volume":"6","author":"Izquierdo","year":"2000","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1124\/mol.64.5.1189","article-title":"Ceramide is involved in R(+)-methanandamide-induced cyclooxygenase-2 expression in human neuroglioma cells","volume":"64","author":"Ramer","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1124\/mol.104.002618","article-title":"Up-regulation of cyclooxygenase-2 expression is involved in R(+)-methanandamide-induced apoptotic death of human neuroglioma cells","volume":"66","author":"Hinz","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1096\/fj.06-6638fje","article-title":"Cannabinoid receptors as novel targets for the treatment of melanoma","volume":"20","author":"Carracedo","year":"2006","journal-title":"FASEB J."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/1476-4598-9-196","article-title":"Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition","volume":"9","author":"Caffarel","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6076","DOI":"10.1016\/j.febslet.2006.09.074","article-title":"Anandamide inhibits Cdk2 and activates Chk1 leading to cell cycle arrest in human breast cancer cells","volume":"580","author":"Laezza","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1172\/JCI37948","article-title":"Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells","volume":"119","author":"Salazar","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1038\/cdd.2011.32","article-title":"Anti-tumoural action of cannabinoids on hepatocellular carcinoma, role of AMPK-dependent activation of autophagy","volume":"18","author":"Vara","year":"2011","journal-title":"Cell Death Differ."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e618","DOI":"10.1038\/cddis.2013.141","article-title":"Involvement of PPAR\u03b3 in the antitumoural action of cannabinoids on hepatocellular carcinoma","volume":"4","author":"Vara","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1038\/jid.2015.45","article-title":"Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death","volume":"135","author":"Armstrong","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1038\/s41598-020-59468-4","article-title":"Inhibition of autophagic flux differently modulates cannabidiol-induced death in 2D and 3D glioblastoma cell cultures","volume":"10","author":"Ivanov","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1002\/ijc.29573","article-title":"Cannabidiol stimulates Aml-1a-dependent glial differentiation and inhibits glioma stem-like cells proliferation by inducing autophagy in a TRPV2-dependent manner","volume":"137","author":"Nabissi","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1158\/1535-7163.MCT-10-1100","article-title":"Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy","volume":"10","author":"Shrivastava","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/s41419-019-2024-0","article-title":"Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia","volume":"10","author":"Pottosin","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"20622","DOI":"10.1038\/s41598-020-77674-y","article-title":"Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma","volume":"10","author":"Go","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1096\/fj.04-1754fje","article-title":"A new strategy to block tumor growth by inhibiting endocannabinoid inactivation","volume":"18","author":"Bifulco","year":"2004","journal-title":"FASEB J."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00109-007-0248-4","article-title":"Increased endocannabinoid levels reduce the development of precancerous lesions in the mouse colon","volume":"86","author":"Izzo","year":"2008","journal-title":"J. Mol. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ejphar.2013.08.039","article-title":"Anticancer activity of anandamide in human cutaneous melanoma cells","volume":"718","author":"Adinolfi","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Hamtiaux, L., Masquelier, J., Muccioli, G.G., Bouzin, C., Feron, O., Gallez, B., and Lambert, D.M. (2012). The association of N-palmitoylethanolamine with the FAAH inhibitor URB597 impairs melanoma growth through a supra-additive action. BMC Cancer, 12.","DOI":"10.1186\/1471-2407-12-92"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.18632\/oncotarget.1723","article-title":"FAAH inhibition enhances anandamide mediated anti-tumorigenic effects in non-small cell lung cancer by downregulating the EGF\/EGFR pathway","volume":"5","author":"Ravi","year":"2014","journal-title":"Oncotarget"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"15047","DOI":"10.18632\/oncotarget.7592","article-title":"Fatty acid amide hydrolase inhibitors confer anti-invasive and antimetastatic effects on lung cancer cells","volume":"7","author":"Winkler","year":"2016","journal-title":"Oncotarget"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1111\/j.1476-5381.2011.01407.x","article-title":"Inhibition of monoacylglycerol lipase attenuates vomiting in Suncus murinus and 2-arachidonoyl glycerol attenuates nausea in rats","volume":"165","author":"Sticht","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.chembiol.2011.05.009","article-title":"Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer","volume":"18","author":"Nomura","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"19593","DOI":"10.1038\/s41598-019-55985-z","article-title":"Lipid accumulation and oxidation in glioblastoma multiforme","volume":"9","author":"Aboussalah","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.3892\/mmr.2016.4829","article-title":"Monoacylglycerol lipase inhibitor JZL184 regulates apoptosis and migration of colorectal cancer cells","volume":"13","author":"Ma","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1158\/1535-7163.MCT-20-0589","article-title":"The Monoacylglycerol Lipase Inhibitor JZL184 Inhibits Lung Cancer Cell Invasion and Metastasis via the CB1 Cannabinoid Receptor","volume":"20","author":"Ramer","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Cipriano, M., Gouveia-Figueira, S., Persson, E., Nording, M., and Fowler, C.J. (2014). The influence of monoacylglycerol lipase inhibition upon the expression of epidermal growth factor receptor in human PC-3 prostate cancer cells. BMC Res. Notes, 7.","DOI":"10.1186\/1756-0500-7-441"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.ejps.2011.11.011","article-title":"Dual inhibition of MAGL and type II topoisomerase by N-phenylmaleimides as a potential strategy to reduce neuroblastoma cell growth","volume":"45","author":"Matuszak","year":"2012","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.chembiol.2009.09.012","article-title":"Discovery of potent and reversible monoacylglycerol lipase inhibitors","volume":"16","author":"King","year":"2009","journal-title":"Chem. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/s41419-020-2425-0","article-title":"Identification of a novel tumor angiogenesis inhibitor targeting Shh\/Gli1 signaling pathway in Non-small cell lung cancer","volume":"11","author":"Lei","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41420-019-0208-0","article-title":"Pristimerin induces apoptosis and autophagy via activation of ROS\/ASK1\/JNK pathway in human breast cancer in vitro and in vivo","volume":"5","author":"Zhao","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"8826","DOI":"10.1158\/0008-5472.CAN-04-3136","article-title":"2-arachidonoylglycerol: A novel inhibitor of androgen-independent prostate cancer cell invasion","volume":"64","author":"Nithipatikom","year":"2004","journal-title":"Cancer Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.3892\/mmr.2015.4721","article-title":"Anti-carcinogenic activity of anandamide on human glioma in vitro and in vivo","volume":"13","author":"Ma","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.yexcr.2005.10.024","article-title":"Anandamide inhibits adhesion and migration of breast cancer cells","volume":"312","author":"Grimaldi","year":"2006","journal-title":"Exp. Cell Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1093\/jnci\/djm268","article-title":"Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases-1","volume":"100","author":"Ramer","year":"2008","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.bcp.2009.11.007","article-title":"Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1","volume":"79","author":"Ramer","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1096\/fj.11-198184","article-title":"Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1","volume":"26","author":"Ramer","year":"2012","journal-title":"FASEB J."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1158\/0008-5472.CAN-07-5176","article-title":"Cannabinoids inhibit glioma cell invasion by down-regulating matrix metalloproteinase-2 expression","volume":"68","author":"Salazar","year":"2008","journal-title":"Cancer Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3109\/15376516.2012.730559","article-title":"Evaluation of anti-invasion effect of cannabinoids on human hepatocarcinoma cells","volume":"23","author":"Pourkhalili","year":"2013","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1007\/s11095-010-0219-2","article-title":"Decrease of plasminogen activator inhibitor-1 may contribute to the anti-invasive action of cannabidiol on human lung cancer cells","volume":"27","author":"Ramer","year":"2010","journal-title":"Pharm. Res."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Pietrovito, L., Iozzo, M., Bacci, M., Giannoni, E., and Chiarugi, P. (2020). Treatment with Cannabinoids as a Promising Approach for Impairing Fibroblast Activation and Prostate Cancer Progression. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030787"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1158\/1535-7163.MCT-07-0371","article-title":"Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells","volume":"6","author":"McAllister","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1158\/0008-5472.CAN-12-1943","article-title":"Id-1 is a key transcriptional regulator of glioblastoma aggressiveness and a novel therapeutic target","volume":"73","author":"Soroceanu","year":"2013","journal-title":"Cancer Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s10549-010-1177-4","article-title":"Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation invasion and metastasis","volume":"129","author":"McAllister","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"4464","DOI":"10.1111\/bph.12803","article-title":"Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer","volume":"171","author":"Murase","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1172\/JCI200316116","article-title":"Inhibition of skin tumour growth and angiogenesis in vivo by activation of cannabinoid receptors","volume":"111","author":"Casanova","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_149","first-page":"529","article-title":"Inhibition of tumor angiogenesis by cannabinoids","volume":"17","author":"Casanova","year":"2003","journal-title":"FASEB J."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"5617","DOI":"10.1158\/0008-5472.CAN-03-3927","article-title":"Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas","volume":"64","author":"Alvarez","year":"2004","journal-title":"Cancer Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.bcp.2014.06.017","article-title":"Cannabinoids inhibit angiogenic capacities of endothelial cells via release of tissue inhibitor of matrix metalloproteinases-1 from lung cancer cells","volume":"91","author":"Ramer","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1002\/JLB.3A0520-187R","article-title":"LPS-mediated neutrophil VEGF-A release is modulated by cannabinoid receptor activation","volume":"109","author":"Braile","year":"2021","journal-title":"J. Leukoc. Biol."},{"key":"ref_153","first-page":"8","article-title":"Anandamide inhibits breast tumor-induced angiogenesis","volume":"10","author":"Picardi","year":"2014","journal-title":"Transl. Med. UniSa."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.phrs.2017.02.002","article-title":"Pharmacological inhibition of MAGL attenuates experimental colon carcinogenesis","volume":"119","author":"Pagano","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1038\/s41598-020-59827-1","article-title":"Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans","volume":"10","author":"Hu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Yang, Y., Huynh, N., Dumesny, C., Wang, K., He, H., and Nikfarjam, M. (2020). Cannabinoids Inhibited Pancreatic Cancer via P-21 Activated Kinase 1 Mediated Pathway. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218035"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.lfs.2015.04.003","article-title":"Differential role of cannabinoids in the pathogenesis of skin cancer","volume":"138","author":"Glodde","year":"2015","journal-title":"Life Sci."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.bcp.2014.07.014","article-title":"Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1","volume":"92","author":"Haustein","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"373","DOI":"10.4049\/jimmunol.165.1.373","article-title":"\u0394-9-tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway","volume":"165","author":"Zhu","year":"2000","journal-title":"J. Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.4049\/jimmunol.174.6.3281","article-title":"\u0394-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response","volume":"174","author":"McKallip","year":"2005","journal-title":"J. Immunol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"574277","DOI":"10.3389\/fonc.2020.574277","article-title":"Targeting CYP2J2 to Enhance the Anti-Glioma Efficacy of Cannabinoid Receptor 2 Stimulation by Inhibiting the Pro-Angiogenesis Function of M2 Microglia","volume":"10","author":"Lei","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"15556","DOI":"10.1038\/s41598-020-72688-y","article-title":"The fatty-acid amide hydrolase inhibitor URB597 inhibits MICA\/B shedding","volume":"10","author":"Sekiba","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1038\/s41467-020-16789-2","article-title":"ARS2\/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages","volume":"11","author":"Yin","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s00223-020-00689-0","article-title":"JZL184, A Monoacylglycerol Lipase Inhibitor, Induces Bone Loss in a Multiple Myeloma Model of Immunocompetent Mice","volume":"107","author":"Marino","year":"2020","journal-title":"Calcif. Tissue Int."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1111\/bph.14426","article-title":"Anti-tumour actions of cannabinoids","volume":"176","author":"Hinz","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1136\/bmj.323.7303.16","article-title":"Cannabinoids for control of chemotherapy induced nausea and vomiting: Quantitative systematic review","volume":"323","author":"Carroll","year":"2001","journal-title":"BMJ"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"7091","DOI":"10.1523\/JNEUROSCI.0403-12.2012","article-title":"Cannabinoid type-1 receptor reduces pain and neurotoxicity produced by chemotherapy","volume":"32","author":"Khasabova","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"20270","DOI":"10.1073\/pnas.0909411106","article-title":"Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivo","volume":"106","author":"Long","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1124\/jpet.117.245704","article-title":"Monoacylglycerol Lipase Inhibitors Reverse Paclitaxel-Induced Nociceptive Behavior and Proinflammatory Markers in a Mouse Model of Chemotherapy-Induced Neuropathy","volume":"366","author":"Curry","year":"2018","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-pharmtox-030220-112741","article-title":"Targeting Endocannabinoid Signaling: FAAH and MAG Lipase Inhibitors","volume":"61","author":"Straub","year":"2021","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1124\/jpet.108.150136","article-title":"Endocannabinoid modulation of scratching response in an acute allergenic model: A new prospective neural therapeutic target for pruritus","volume":"329","author":"Schlosburg","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1126\/science.aaf7497","article-title":"Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474","volume":"356","author":"Janssen","year":"2017","journal-title":"Science"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"e131","DOI":"10.1161\/CIR.0000000000000883","article-title":"Medical Marijuana, Recreational Cannabis, and Cardiovascular Health: A Scientific Statement From the American Heart Association","volume":"142","author":"Page","year":"2020","journal-title":"Circulation"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nm1421","article-title":"CB1 cannabinoid receptor antagonism: A new strategy for the treatment of liver fibrosis","volume":"12","author":"Julien","year":"2006","journal-title":"Nat. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/sj.bjc.6603236","article-title":"A pilot study of \u03949-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme","volume":"95","author":"Duarte","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1038\/s41416-021-01259-3","article-title":"GWCA1208 study group. A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma","volume":"124","author":"Twelves","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_177","unstructured":"U.S. National Library of Medicine (2021, October 20). ClinicalTrials.gov: A Phase I\/Ib Study on the Safety of Epidiolex in Patients with Prostate Cancer with Rising PSA after Localized Therapy with Either Surgery or Radiation, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04428203?term=CBD&cond=cancer&draw=2&rank=2."},{"key":"ref_178","unstructured":"U.S. National Library of Medicine (2021, October 20). ClinicalTrials.gov: Why Antiprogestrone (Mifepristone) and Cyp 26 Inhibitor Must Be Combined with Tamoxifen or (Tamoxifen and Retinoic Acid) for Treating Early Breast Cancer, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05016349?term=CBD&cond=cancer&draw=1&rank=5."},{"key":"ref_179","unstructured":"U.S. National Library of Medicine (2021, October 20). ClinicalTrials.gov: Phase Ib, Open-Label, Multicenter, Intrapatient Dose-Escalation Clinical Trial to Assess the Safety Profile of the TN-TC11G (THC+CBD) Combination with Temozolomide and Radiotherapy in Patients with Newly-Diagnosed Glioblastoma, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03529448?term=CBD&cond=cancer&draw=3&rank=42."},{"key":"ref_180","unstructured":"U.S. Food and Drug Administration (2021, October 20). FDA News Release, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-warns-companies-marketing-unproven-products-derived-marijuana-claim-treat-or-cure-cancer."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/22\/5701\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:30:12Z","timestamp":1760167812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/22\/5701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,15]]},"references-count":180,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["cancers13225701"],"URL":"https:\/\/doi.org\/10.3390\/cancers13225701","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,15]]}}}