Cannabinoids as a Promising Therapeutic Approach for the Treatment of Glioblastoma Multiforme: A Literature Review
International Clinical Neuroscience Journal,
Vol. 3 No. 3 (2016),
7 December 2016
,
Page 138-143
https://doi.org/10.22037/icnj.v3i3.13655
Abstract
Gliobalstoma multiforme (GBM) or grade 4 astrocytoma is the most malignant form of primary brain tumor. Treatment of glioblastoma is difficult despite of surgery, radiotherapy and chemotherapy. Patients with glioblastoma survive for less than 12 months. Considering to biology function of glioblastoma, researchers have recently offered new therapeutic approaches such as cannabinoid therapy for glioblastoma. Cannabinoids are active compounds of Cannabis sativa that operate in the body similar to endogenous canabinoids –the endocannabinoids- through cell surface receptors. It is interesting that cannabinoids could exert a wide spectrum from antiproliferative effects in condition of the cell culture, animal models of glioblastoma and clinical trials. As a result, Cannabinoids seem to modulate intracellular signaling pathways and the endoplasmic reticulum stress response in glioma cells. Those play antitumoral effects through apoptosis induction and inhibition of glioblastoma angiogenesis. The goal of this study was to discuss cannabinoid therapy and also what cellular mechanisms are involved in the tumoricidal effect of the cannabinoids. In this review article, we will focus on cannabinoids, their receptor dependent functional roles against glioblastoma acccording to growth, angiogenesis, metastasis, and future purposes in exploring new possible therapeutic opportunities.
- Cannabinoids
- Glioblastoma multiforme
- Apoptosis
- Angiogenesis inhibitors
- Clinical trial
How to Cite
References
Furnari FB, Fenton T, Bachoo RM, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes dev. 2007;21:2683–710.
Louis D, Ohgaki H, Wiestler O. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109.
Louis DN, Ohgaki H, Wiestler OD, et al. WHO Classification of Tumours of the Central Nervous System. 4th ed. International Agency for Research on Cancer Lyon; 2007.
Ostrom QT, Gittleman H, Liao P, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro Oncol. 2014;16:1-63.
Lang MF, Yang S, Zhao C, et al. Genome-wide profiling identified a set of miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. PLoS One. 2012;7:e36248.
Koul D, Shen R, Bergh S, et al. Targeting integrin-linked kinase inhibits Akt signaling pathways and decreases tumor progression of human glioblastoma. Mol cancer ther. 2005;4:1681.
Wick W, Naumann U, Weller M. Transforming growth factor-beta: A molecular target for the future therapy of glioblastoma. Curr pharma des. 2006;12:341–49.
Okada H, Kohanbash G, Zhu X, et al. Immunotherapeutic approaches for glioma. Crit Rev Immunol. 2009;29:1-42.
de Bono JS, Ashworth A. Translating cancer research into targeted therapeutics. Nature. 2010; 467:543-9.
Guzmán M, Galve-Roperh I, Sánchez C. Ceramide: a new second messenger of cannabinoid action. Trends Pharmacol Sci. 2001;22:19-22. 11. Sánchez C, de Ceballos ML, Gomez del Pulgar T, Rueda D, Corbacho C, Velasco G, et al. Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor. Cancer Res. 2001;61:5784-9.
Pertwee RG. Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br J Pharmacol. 2009;156:397-411.
Gómez-Ruiz M, Hernández M, de Miguel R, et al. An overview on the biochemistry of the cannabinoid system. Mol Neurobiol. 2007;36:3-14.
Fowler C. The pharmacology of the cannabinoid system -a question of efficacy and selectivity. Mol Neurobiol. 2007;36:15-25.
Howlett AC, Barth F, Bonner TI, et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev. 2002; 54:161–202.
Piomelli D. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci. 2003; 4:873–884.
Fernandez-Ruiz J, Romero J, Velasco G, et al. Cannabinoid CB2 receptor: a new target for controlling neural cell survival? Trends Pharmacol Sci. 2007; 28:83–92.
Malfitano AM, Ciaglia E, Gangemi G, et al. Update on the endocannabinoid system as an anticancer target. Expert Opin Ther Targets. 2011;15:297–308.
Liu J, Gao B, Mirshahi F, et al. Functional CB1 cannabinoid receptors in human vascular endothelial cells. Biochem J. 2000;346:835–840.
Rueda D, Galve-Roperh I, Haro A, et al. The CB1cannabinoid receptor is coupled to the activation of c-Jun Nterminal kinase. Mol Pharmacol. 2000;58:814–20.
Bouaboula M, Poinot-Chazel C, Bourrie B, et al. Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. Biochem J. 1995;312:637–641.
Derkinderen P, Toutant M, Burgaya F, et al. Regulation of a neuronal form of focal adhesion kinase by anandamide. Science. 1996;273:1719–22.
Gomez del Pulgar T, Velasco G, Guzman M. The CB1 cannabinoid receptor is coupled to the activation of protein kinase B/Akt. Biochem J. 2000;347:369–73.
Sanchez C, Rueda D, Segui B, et al. The CB1 cannabinoid receptor of astrocytes is coupled to sphingomyelin hydrolysis through the adaptor protein fan. Mol Pharmacol. 2001;59:955–59.
Guzman M. Cannabinoids: potential anticancer agents. Nat Rev Cancer. 2003;3:745–55.
Hall W, Christie M, Currow D. Cannabinoids and cancer: causation, remediation, and palliation. Lancet Oncol. 2005; 6:35–42.
Sanchez C, Galve-Roperh I, Canova C, et al. Delta9-tetrahydrocannabinol induces apoptosis in C6 glioma cells. FEBS Lett. 1998;436:6–10.
Galve-Roperh I, Sanchez C, Cortes ML, et al. Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nat Med. 2000;6:313–319.
Ellert-Miklaszewska A, Ciechomska I, Kaminska B. Cannabinoid signaling in glioma cells. Adv Exp Med Biol. 2013;986:209-20.
Ogretmen B, Hannun YA. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer. 2004;4:604–616.
Riboni L, Campanella R, Bassi R, et al. Ceramide levels are inversely associated with malignant progression of human glial tumors. Glia. 2002;39:105-13.
Verfaillie T, Salazar M, Velasco G, et al. Linking ER stress to autophagy: potential implications for cancer therapy. Int J Cell Biol. 2010;1-19.
Mizushima N, Levine B, Cuervo AM, et al. Autophagy fights disease through cellular self-digestion. Nature. 2008;451:1069–75.
Eisenberg-Lerner A, Bialik S, Simon HU, et al. Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ. 2009;16:966–975.
Salazar M, Carracedo A, Salanueva IJ, et al. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J. Clin. Invest. 2009;119:1359–72.
Carracedo A, Lorente M, Egia A, et al. The stress regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell. 2006;9:301–312.
Ellert-Miklaszewska A, Kaminska B, Konarska L. Cannabinoids down-regulate PI3K/Akt and Erk signalling pathways and activate proapoptotic function of Bad protein. Cell Signal. 2005;17:25–37.
Herrera B, Carracedo A, Diez-Zaera M, et al. The CB2 cannabinoid receptor signals apoptosis via ceramide-dependent activation of the mitochondrial intrinsic pathway. Exp. Cell Res. 2006;312:2121–2131.
Eisenberg-Lerner A, Bialik S, Simon HU, et al, Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ. 2009;16:966–975.
Gómez del Pulgar T, Velasco G, Sánchez C, et al. De novo-synthesized ceramide is involved in cannabinoid-induced apoptosis. Biochem J. 2002;363:183-8.
Massi P, Vaccani A, Ceruti S, et al. Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. J Pharmacol Exp Ther. 2004;308:838-45.
Recht LD, Salmonsen R, Rosetti R, et al. Antitumor effects of ajulemic acid (CT3), a synthetic non-psychoactive cannabinoid. Biochem Pharmacol. 2001; 62:755-63.
Cudaback E, Marrs W, Moeller T, et al. The expression level of CB1 and CB2 receptors determines their efficacy at inducing apoptosis in astrocytomas. PLoS ONE. 2010;5:e8702.
Day TA, Rakhshan F, Deutsch DG, et al. Role of fatty acid amide hydrolase in the transport of the endogenous cannabinoid annandamide. Mol Pharmacol. 2001;59:1369-75.
Blazquez C, Casanova ML, Planas A, et al. Inhibition of tumor angiogenesis by cannabinoids. FASEB J. 2003;17:529–31.
Portella G, Laezza C, Laccetti P, et al. Inhibitory effects of cannabinoid CB1 receptor stimulation on tumor growth and metastatic spreading: actions on signals involved in angiogenesis and metastasis. FASEB J. 2003;17:1771–73.
Blazquez C, Gonzalez-Feria L, Alvarez L, et al. Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas. Cancer Res. 2004;64:5617–23.
Hernán Pérez de la Ossa D, Lorente M, Gil-Alegre ME, et al. Local Delivery of Cannabinoid-Loaded Microparticles Inhibits Tumor Growth in a Murine Xenograft Model of Glioblastoma Multiforme. PLoS One. 2013;8:e54795.
Kogan NM, Blazquez C, Alvarez L, et al. cannabinoid quinine inhibits angiogenesis by targeting vascular endothelial cells. Mol Pharmacol. 2006;70:51–59.
Blázquez C, Salazar M, Carracedo A, et al. Cannabinoids inhibit glioma cell invasion by down-regulating matrix metalloproteinase 2 expression. Cancer Res. 2008;68:1945–52.
Preet A, Ganju RK, Groopman JE. Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene. 2008;27:339–46.
Lauffenburger DA, Horwitz AF. Cell migration: a physically integrated molecular process. Cell. 1996;84:359–69.
Blázquez C, Carracedo A, Salazar M, et al. Down-regulation of tissue inhibitor of metalloproteinases-1 in glioma: a new marker of cannabinoid antitumoral activity? Neuropharmacol. 2008;54:235-43.
Guzmán M, Duarte MJ, Blázquez C, et al. A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br. J. Cancer. 2006;95:197–203.
Costa L, Amaral C, Teixeira N, et al. Cannabinoid-induced autophagy: protective or death role? Prostaglandins Other Lipid Mediat. 2016;122:54-63.
Torres S, Lorente M, Rodríguez-Fornés F, et al. A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol. Cancer Ther. 2011;10:90–103.
Velasco G, Hernández-Tiedra S, Dávila D, et al. The use of cannabinoids as anticancer agents. Pro Neuro-Psychopharmacol Biol Psych. 2016;64: 259–66.
Marcu JP, Christian RT, Lau D, et al. Cannabidiol enhances the inhibitory effects of Δ9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol. Cancer Ther. 2010;9:180–9.
Sa´nchez C, de Ceballos ML, Go´mez del Pulgar T, et al. Inhibition of gliomagrowth in vivo by selective activation of the CB2 cannabinoid receptor. Cancer Res. 2001;61:5784–89.
Zhu LX, Sharma S, Stolina M, et al. Δ9-Tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokinedependent pathway. J Immunol. 2000;165:373–80.
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