Towards the use of cannabinoids as antitumour agents (original) (raw)

• Gaoni, Y. & Mechoulam, R. Isolation, structure and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc. 86, 1646–1647 (1964).
  Article CAS Google Scholar
• Pertwee, R. G. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br. J. Pharmacol. 153, 199–215 (2008).
  Article CAS PubMed Google Scholar
• Devane, W. A. et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258, 1946–1949 (1992).
  Article CAS PubMed Google Scholar
• Mechoulam, R. et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 50, 83–90 (1995).
  Article CAS PubMed Google Scholar
• Sugiura, T. et al. 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem. Biophys. Res. Commun. 215, 89–97 (1995).
  Article CAS PubMed Google Scholar
• Pertwee, R. G. et al. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol. Rev. 62, 588–631 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C. & Bonner, T. I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346, 561–564 (1990).
  Article CAS PubMed Google Scholar
• Munro, S., Thomas, K. L. & Abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365, 61–65 (1993).
  Article CAS PubMed Google Scholar
• Fernandez-Ruiz, J. et al. Cannabinoid CB2 receptor: a new target for controlling neural cell survival? Trends Pharmacol. Sci. 28, 39–45 (2007).
  Article CAS PubMed Google Scholar
• Atwood, B. K. & Mackie, K. CB2: a cannabinoid receptor with an identity crisis. Br. J. Pharmacol. 160, 467–479 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Guzman, M. et al. A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br. J. Cancer 95, 197–203 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Sarfaraz, S., Adhami, V. M., Syed, D. N., Afaq, F. & Mukhtar, H. Cannabinoids for cancer treatment: progress and promise. Cancer Res. 68, 339–342 (2008).
  Article CAS PubMed Google Scholar
• Katona, I. & Freund, T. F. Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nature Med. 14, 923–930 (2008).
  Article CAS PubMed Google Scholar
• Pacher, P., Batkai, S. & Kunos, G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol. Rev. 58, 389–462 (2006).
  Article CAS PubMed Google Scholar
• Pertwee, R. G. Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br. J. Pharmacol. 156, 397–411 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Guzman, M. Cannabinoids: potential anticancer agents. Nature Rev. Cancer 3, 745–755 (2003).
  Article CAS Google Scholar
• Cudaback, E., Marrs, W., Moeller, T. & Stella, N. The expression level of CB1 and CB2 receptors determines their efficacy at inducing apoptosis in astrocytomas. PLoS ONE 5, e8702 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Hart, S., Fischer, O. M. & Ullrich, A. Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor. Cancer Res. 64, 1943–1950 (2004).
  Article CAS PubMed Google Scholar
• McKallip, R. J., Nagarkatti, M. & Nagarkatti, P. S. Δ9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. J. Immunol. 174, 3281–3289 (2005).
  Article CAS PubMed Google Scholar
• Zhu, L. X. et al. Δ9-tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. J. Immunol. 165, 373–380 (2000).
  Article CAS PubMed Google Scholar
• Malfitano, A. M. et al. Update on the endocannabinoid system as an anticancer target. Expert Opin. Ther. Targets. 15, 297–308 (2011).
  Article CAS PubMed Google Scholar
• Caffarel, M. M., Sarrio, D., Palacios, J., Guzman, M. & Sanchez, C. Δ9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res. 66, 6615–6621 (2006).
  Article CAS PubMed Google Scholar
• Sanchez, C. et al. Inhibition of glioma growth in vivo by selective activation of the CB2 cannabinoid receptor. Cancer Res. 61, 5784–5789 (2001).
  CAS PubMed Google Scholar
• Nomura, D. K. et al. Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell 140, 49–61 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Thors, L. et al. Fatty acid amide hydrolase in prostate cancer: association with disease severity and outcome, CB1 receptor expression and regulation by IL-4. PLoS ONE 5, e12275 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Zheng, D. et al. The cannabinoid receptors are required for ultraviolet-induced inflammation and skin cancer development. Cancer Res. 68, 3992–3998 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Joosten, M. et al. Leukemic predisposition of pSca-1/Cb2 transgenic mice. Exp. Hematol. 30, 142–149 (2002).
  Article CAS PubMed Google Scholar
• Wang, D. et al. Loss of cannabinoid receptor 1 accelerates intestinal tumor growth. Cancer Res. 68, 6468–6476 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Izzo, A. A. et al. Increased endocannabinoid levels reduce the development of precancerous lesions in the mouse colon. J. Mol. Med. (Berl.) 86, 89–98 (2008).
  Article CAS Google Scholar
• Blazquez, C. et al. Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas. Cancer Res. 64, 5617–5623 (2004).
  Article CAS PubMed Google Scholar
• Galve-Roperh, I. et al. Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nature Med. 6, 313–319 (2000).
  Article CAS PubMed Google Scholar
• Gomez del Pulgar, T., Velasco, G., Sanchez, C., Haro, A. & Guzman, M. De novo-synthesized ceramide is involved in cannabinoid-induced apoptosis. Biochem. J. 363, 183–188 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Carracedo, A. et al. The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell 9, 301–312 (2006).
  Article CAS PubMed Google Scholar
• Encinar, J. A. et al. Human p8 is a HMG-I/Y-like protein with DNA binding activity enhanced by phosphorylation. J. Biol. Chem. 276, 2742–2751 (2001).
  Article CAS PubMed Google Scholar
• Schroder, M. & Kaufman, R. J. The mammalian unfolded protein response. Annu. Rev. Biochem. 74, 739–789 (2005).
  Article CAS PubMed Google Scholar
• Verfaillie, T., Salazar, M., Velasco, G. & Agostinis, P. Linking ER stress to autophagy: potential implications for cancer therapy. Int. J. Cell Biol. 2010, 930509 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Mizushima, N., Levine, B., Cuervo, A. M. & Klionsky, D. J. Autophagy fights disease through cellular self-digestion. Nature 451, 1069–1075 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Eisenberg-Lerner, A., Bialik, S., Simon, H. U. & Kimchi, A. Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ. 16, 966–975 (2009).
  Article CAS PubMed Google Scholar
• Salazar, M. et al. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J. Clin. Invest. 119, 1359–1372 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Vara, D. et al. Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy. Cell Death Differ. 18, 1099–1111 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Carracedo, A. et al. Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. Cancer Res. 66, 6748–6755 (2006).
  Article CAS PubMed Google Scholar
• Blazquez, C. et al. Cannabinoid receptors as novel targets for the treatment of melanoma. FASEB J. 20, 2633–2635 (2006).
  Article CAS PubMed Google Scholar
• Sarfaraz, S., Afaq, F., Adhami, V. M., Malik, A. & Mukhtar, H. Cannabinoid receptor agonist-induced apoptosis of human prostate cancer cells LNCaP proceeds through sustained activation of ERK1/2 leading to G1 cell cycle arrest. J. Biol. Chem. 281, 39480–39491 (2006).
  Article CAS PubMed Google Scholar
• Guindon, J. & Hohmann, A. G. The endocannabinoid system and cancer: therapeutic implication. Br. J. Pharmacol. 163, 1447–1463 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Ligresti, A. et al. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J. Pharmacol. Exp. Ther. 318, 1375–1387 (2006).
  Article CAS PubMed Google Scholar
• Massi, P. et al. 5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid. J. Neurochem. 104, 1091–1100 (2008).
  Article CAS PubMed Google Scholar
• Shrivastava, A., Kuzontkoski, P. M., Groopman, J. E. & Prasad, A. Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Mol. Cancer Ther. 10, 1161–1172 (2011).
  Article CAS PubMed Google Scholar
• Massi, P. et al. The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells. Cel. Mol. Life Sci. 63, 2057–2066 (2006).
  Article CAS Google Scholar
• Casanova, M. L. et al. Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J. Clin. Invest. 111, 43–50 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Blazquez, C. et al. Inhibition of tumor angiogenesis by cannabinoids. FASEB J. 17, 529–531 (2003).
  Article CAS PubMed Google Scholar
• Portella, G. 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. 17, 1771–1773 (2003).
  Article CAS PubMed Google Scholar
• Pisanti, S. et al. Antiangiogenic activity of the endocannabinoid anandamide: correlation to its tumor-suppressor efficacy. J. Cell Physiol. 211, 495–503 (2007).
  Article CAS PubMed Google Scholar
• Blazquez, C. et al. Cannabinoids inhibit glioma cell invasion by down-regulating matrix metalloproteinase-2 expression. Cancer Res. 68, 1945–1952 (2008).
  Article CAS PubMed Google Scholar
• Grimaldi, C. et al. Anandamide inhibits adhesion and migration of breast cancer cells. Exp. Cell Res. 312, 363–373 (2006).
  Article CAS PubMed Google Scholar
• Qamri, Z. et al. Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Mol. Cancer Ther. 8, 3117–3129 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Preet, A., Ganju, R. K. & Groopman, J. E. Δ9-tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene 27, 339–346 (2008).
  Article CAS PubMed Google Scholar
• Ramer, R. & Hinz, B. Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases-1. J. Natl. Cancer Inst. 100, 59–69 (2008).
  Article CAS PubMed Google Scholar
• McAllister, S. D., Christian, R. T., Horowitz, M. P., Garcia, A. & Desprez, P. Y. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. Mol. Cancer Ther. 6, 2921–2927 (2007).
  Article CAS PubMed Google Scholar
• McAllister, S. D. et al. Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. Breast Cancer Res. Treat. 129, 37–47 (2011).
  Article CAS PubMed Google Scholar
• Galve-Roperh, I., Aguado, T., Palazuelos, J. & Guzman, M. Mechanisms of control of neuron survival by the endocannabinoid system. Curr. Pharm. Des. 14, 2279–2288 (2008).
  Article CAS PubMed Google Scholar
• Chan, P. C., Sills, R. C., Braun, A. G., Haseman, J. K. & Bucher, J. R. Toxicity and carcinogenicity of Δ9-tetrahydrocannabinol in Fischer rats and B6C3F1 mice. Fundam. Appl. Toxicol. 30, 109–117 (1996).
  Article CAS PubMed Google Scholar
• Lombard, C., Nagarkatti, M. & Nagarkatti, P. CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: potential role for CB2-selective ligands as immunosuppressive agents. Clin. Immunol. 122, 259–270 (2007).
  Article CAS PubMed Google Scholar
• Rieder, S. A., Chauhan, A., Singh, U., Nagarkatti, M. & Nagarkatti, P. Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression. Immunobiology 215, 598–605 (2010).
  Article CAS PubMed Google Scholar
• Lorente, M. et al. Stimulation of the midkine/ALK axis renders glioma cells resistant to cannabinoid antitumoral action. Cell Death Differ. 18, 959–973 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Newton, C. A., Chou, P. J., Perkins, I. & Klein, T. W. CB1 and CB2 cannabinoid receptors mediate different aspects of Δ9-tetrahydrocannabinol (THC)-induced T helper cell shift following immune activation by Legionella pneumophila infection. J. Neuroimmune Pharmacol. 4, 92–102 (2009).
  Article PubMed Google Scholar
• Lu, T., Newton, C., Perkins, I., Friedman, H. & Klein, T. W. Cannabinoid treatment suppresses the T-helper cell-polarizing function of mouse dendritic cells stimulated with Legionella pneumophila infection. J. Pharmacol. Exp. Ther. 319, 269–276 (2006).
  Article CAS PubMed Google Scholar
• Steffens, S. et al. Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature 434, 782–786 (2005).
  Article CAS PubMed Google Scholar
• Hegde, V. L., Nagarkatti, M. & Nagarkatti, P. S. Cannabinoid receptor activation leads to massive mobilization of myeloid-derived suppressor cells with potent immunosuppressive properties. Eur. J. Immunol. 40, 3358–3371 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Burstein, S. H. & Zurier, R. B. Cannabinoids, endocannabinoids, and related analogs in inflammation. AAPS J. 11, 109–119 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Liu, W. M., Fowler, D. W. & Dalgleish, A. G. Cannabis-derived substances in cancer therapy--an emerging anti-inflammatory role for the cannabinoids. Curr. Clin. Pharmacol. 5, 281–287 (2010).
  Article CAS PubMed Google Scholar
• Hudson, B. D., Hebert, T. E. & Kelly, M. E. Ligand- and heterodimer-directed signaling of the CB1 cannabinoid receptor. Mol. Pharmacol. 77, 1–9 (2010).
  Article CAS PubMed Google Scholar
• Dainese, E., Oddi, S. & Maccarrone, M. Interaction of endocannabinoid receptors with biological membranes. Curr. Med. Chem. 17, 1487–1499 (2010).
  Article CAS PubMed Google Scholar
• Smith, T. H., Sim-Selley, L. J. & Selley, D. E. Cannabinoid CB1 receptor-interacting proteins: novel targets for central nervous system drug discovery? Br. J. Pharmacol. 160, 454–466 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Mirkin, B. L. et al. Identification of midkine as a mediator for intercellular transfer of drug resistance. Oncogene 24, 4965–4974 (2005).
  Article CAS PubMed Google Scholar
• Kadomatsu, K. The midkine family in cancer, inflammation and neural development. Nagoya J. Med. Sci. 67, 71–82 (2005).
  CAS PubMed Google Scholar
• Palmer, R. H., Vernersson, E., Grabbe, C. & Hallberg, B. Anaplastic lymphoma kinase: signalling in development and disease. Biochem. J. 420, 345–361 (2009).
  Article CAS PubMed Google Scholar
• de Bono, J. S. & Ashworth, A. Translating cancer research into targeted therapeutics. Nature 467, 543–549 (2010).
  Article CAS PubMed Google Scholar
• Grande, E., Bolos, M. V. & Arriola, E. Targeting oncogenic ALK: a promising strategy for cancer treatment. Mol. Cancer Ther. 10, 569–579 (2011).
  Article CAS PubMed Google Scholar
• Lorente, M. et al. Amphiregulin is a factor for resistance of glioma cells to cannabinoid-induced apoptosis. Glia 57, 1374–1385 (2009).
  Article PubMed Google Scholar
• Torres, S. et al. A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol. Cancer Ther. 10, 90–103 (2011).
  Article CAS PubMed Google Scholar
• Donadelli, M. et al. Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism. Cell Death Dis. 2, e152 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Miyato, H. et al. Pharmacological synergism between cannabinoids and paclitaxel in gastric cancer cell lines. J. Surg. Res. 155, 40–47 (2009).
  Article CAS PubMed Google Scholar
• Gustafsson, S. B., Lindgren, T., Jonsson, M. & Jacobsson, S. O. Cannabinoid receptor-independent cytotoxic effects of cannabinoids in human colorectal carcinoma cells: synergism with 5-fluorouracil. Cancer Chemother. Pharmacol. 63, 691–701 (2009).
  Article CAS PubMed Google Scholar
• Marcu, J. P. et al. Cannabidiol enhances the inhibitory effects of Δ9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol. Cancer Ther. 9, 180–189 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Bifulco, M. et al. Control by the endogenous cannabinoid system of ras oncogene-dependent tumor growth. FASEB J. 15, 2745–2747 (2001).
  Article CAS PubMed Google Scholar
• Herrera, B. et al. The CB2 cannabinoid receptor signals apoptosis via ceramide-dependent activation of the mitochondrial intrinsic pathway. Exp. Cell Res. 312, 2121–2131 (2006).
  Article CAS PubMed Google Scholar
• Du, K., Herzig, S., Kulkarni, R. N. & Montminy, M. TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science 300, 1574–1577 (2003).
  Article CAS PubMed Google Scholar
• 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. 17, 25–37 (2005).
  Article CAS PubMed Google Scholar
• Caffarel, M. M. et al. JunD is involved in the antiproliferative effect of Δ9-tetrahydrocannabinol on human breast cancer cells. Oncogene 27, 5033–5044 (2008).
  Article CAS PubMed Google Scholar
• Lonardi, S., Tosoni, A. & Brandes, A. A. Adjuvant chemotherapy in the treatment of high grade gliomas. Cancer Treat. Rev. 31, 79–89 (2005).
  Article CAS PubMed Google Scholar
• Nieder, C., Adam, M., Molls, M. & Grosu, A. L. Therapeutic options for recurrent high-grade glioma in adult patients: recent advances. Crit. Rev. Oncol. Hematol. 60, 181–193 (2006).
  Article PubMed Google Scholar
• Purow, B. & Schiff, D. Advances in the genetics of glioblastoma: are we reaching critical mass? Nature Rev. Neurol. 5, 419–426 (2009).
  Article CAS Google Scholar
• Stupp, R. et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352, 987–996 (2005).
  Article CAS PubMed Google Scholar
• Caffarel, M. M. et al. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Mol. Cancer 9, 196 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Oesch, S. et al. Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma. Mol. Cancer Ther. 8, 1838–1845 (2009).
  Article CAS PubMed Google Scholar
• Gustafsson, K., Christensson, B., Sander, B. & Flygare, J. Cannabinoid receptor-mediated apoptosis induced by R(+)-methanandamide and Win55,212-2 is associated with ceramide accumulation and p38 activation in mantle cell lymphoma. Mol. Pharmacol. 70, 1612–1620 (2006).
  Article CAS PubMed Google Scholar
• McKallip, R. J. et al. Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease. Blood 100, 627–634 (2002).
  Article CAS PubMed Google Scholar
• Jia, W. et al. Δ9-tetrahydrocannabinol-induced apoptosis in Jurkat leukemia T cells is regulated by translocation of Bad to mitochondria. Mol. Cancer Res. 4, 549–562 (2006).
  Article CAS PubMed Google Scholar
• Mimeault, M., Pommery, N., Wattez, N., Bailly, C. & Henichart, J. P. Anti-proliferative and apoptotic effects of anandamide in human prostatic cancer cell lines: implication of epidermal growth factor receptor down-regulation and ceramide production. Prostate 56, 1–12 (2003).
  Article CAS PubMed Google Scholar
• Olea-Herrero, N., Vara, D., Malagarie-Cazenave, S. & Diaz-Laviada, I. Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R(+)-Methanandamide and JWH-015: involvement of CB2 . Br. J. Cancer 101, 940–950 (2009).
  Article CAS PubMed PubMed Central Google Scholar