Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas
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To evaluate, through a systematic review of the literature, the antitumoral effects of cannabinoids on gliomas. Research included the following electronic databases: PUBMED, EMBASE, LILACS and The Cochrane Collaboration Controlled Trials Register. All published studies involving the antitumoral effects (cellular and molecular mechanisms) of cannabinoids were considered for this review. The bibliography search strategy included all publications of each of these databases until December 31, 2012. From 2,260 initially identified articles, 35 fulfilled the inclusion criteria for this review. All the studies included in this systematic review were experimental (in vivo and/or in vitro), except for one pilot clinical trial phase I/II involving humans. In all experimental studies included, cannabinoids exerted antitumoral activity in vitro and/or antitumoral evidence in vivo in several models of tumor cells and tumors. The antitumor activity included: antiproliferative effects (cell cycle arrest), decreased viability and cell death by toxicity, apoptosis, necrosis, autophagy, as well as antiangiogenic and antimigratory effects. Antitumoral evidence included: reduction in tumor size, antiangiogenic, and antimetastatic effects. Additionally, most of the studies described that the canabinnoids exercised selective antitumoral action in several distinct tumor models. Thereby, normal cells used as controls were not affected. The safety factor in the cannabinoids’ administration has also been demonstrated in vivo. The various cannabinoids tested in multiple tumor models showed antitumoral effects both in vitro and in vivo. These findings indicate that cannabinoids are promising compounds for the treatment of gliomas.
KeywordsGliomas Cannabinoids Apoptosis Cell cycle arrest Anti-angiogenesis Anti-metastasis
Coordination of Improvement of People of Higher Level (CAPES), Cochrane Center.
Conflict of interest
This paper has no conflict of interests.
- 3.Mechoulam R, Ben Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, Pertwee RG, Griffin G, Bayewitch M, Barg J, Vogel Z (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90PubMedCrossRefGoogle Scholar
- 18.Blásquez C, Casanova L, Planas A, del Pulgar TG, Villanueva C, Aceñero MJ, Aragonês J, Huffman JW, Jorcano JL, Guzmán M (2003) Inhibition of tumor angiogenesis by cannabinoids. FASEB J 17(Suppl3):529–531Google Scholar
- 22.Carracedo A, Lorente M, Egia A, Blázquez C, Garcia S, Giroux V, Malicet C, Villuendas R, Gironella M, Gonzáliz-Feria L, Piris MA, Iovanna JL, Guzmán M, Velasco G (2006) The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell 9:301–312PubMedCrossRefGoogle Scholar
- 26.Salazar M, Carracedo A, Salanueva IJ, Hernández-Tiedra S, Lorente M, Egia A, Vázquez P, Blázquez C, Torres S, Garcia S, Nowak J, Fimia GM, Piacentini M, Cecconi F, Pandolfi PP, González-Feria L, Iovanna JL, Guzmán M, Boya P, Velasco G (2009) Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest 119:1359–1372PubMedCentralPubMedCrossRefGoogle Scholar
- 28.Soroceanu L, Murase R, Limbad C, Singer E, Allison J, Adrados I, Kawamura R, Pakdel A, Fukuyo Y, Nguyen D, Khan S, Arauz R, Yount GL, Moore DH, Desprez PY, McAllister SD (2013) Id-1 is a key transcriptional regulator of glioblastoma aggressiveness and a novel therapeutic target. Cancer Res 73:1559–1569PubMedCrossRefGoogle Scholar
- 30.Dolecek TA, Propp JM, Stroup NE, Kruchko C (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neurooncology 14(Suppl5):v1–v49Google Scholar
- 45.Ros J, Clària J, To-Figueiras J, Planagumá A, Cejudo-Martín P, Fernández-Varo G, Martín-Ruiz R, Arroyo V, Rivera F, Rodes J, Jiménez W (2002) Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat. Gastroenterology 122:85–93PubMedCrossRefGoogle Scholar
- 52.Marcu JP, Christian RT, Lau D, Zielinski AJ, Horowitz MP, Lee J, Pakdel A, Allison J, Limbad C, Moore DH, Yount GL, Desprez P-Y, McAllister SD (2010) Cannabidiol enhances the inhibitory effects of delta-9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol Cancer Ther 9(Suppl1):180–189PubMedCentralPubMedCrossRefGoogle Scholar
- 60.Macarrone M, Pauselli R, Di Rienzo M, Finazzi-Agró A (2002) Binding, degradation and apoptotic activity of stearoylethanolamide in rat C6 glioma cells. Biochem J 366:137–144Google Scholar
- 61.Fowler CJ, Jonsson KO, Andersson A, Juntunen J, Järvinen T, Vandevoorde S, Lambert DM, Jerman JC, Smart D (2003) 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. Biochem Pharmacol 66:757–767PubMedCrossRefGoogle Scholar