Targeting Cannabinoid Receptors in Brain Tumors
Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endogenous substances — the endocannabinoids — that activate specific cell surface receptors. Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different types of tumor cells, including glioma cells, in laboratory animals. They do so by modulating key cell signaling pathways, mostly the endoplasmic reticulum stress response, thereby inducing antitumoral actions such as the apoptotic death of tumor cells and the inhibition of tumor angiogenesis. Of interest, cannabinoids seem to be selective antitumoral compounds as they kill glioma cells but not their nontransformed astroglial counterparts. On the basis of these preclinical findings, a pilot clinical study of Δ9-tetrahydrocannabinol (Δ9-THC) in patients with recurrent glioblastoma multiforme has been recently run. The fair safety profile of Δ9-THC, together with its possible growth-inhibiting action on tumor cells, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.
KeywordsGlioma Cell Endoplasmic Reticulum Stress Focal Adhesion Kinase Ceramide Accumulation Recurrent Glioblastoma Multiforme
Unable to display preview. Download preview PDF.
- Benali-Furet NL, Chami M, Houel L, De Giorgi F, Vernejoul F, Lagorce D, Buscail L, Bartenschlager R, Ichas F, Rizzuto R, Paterlini-Brechot P (2005) Hepatitis C virus core triggers apoptosis in liver cells by inducing ER stress and ER calcium depletion. Oncogene 24:4921–4933.CrossRefPubMedGoogle Scholar
- Carracedo A, Lorente M, Egia A, Blázquez C, Garcia S, Giroux V, Malicet C, Villuendas R, Gironella M, Gonzalez-Feria L, Piris MA, Iovanna JL, Guzman M, Velasco G (2006b) The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell 9:301–312.CrossRefPubMedGoogle Scholar
- Mallo GV, Fiedler F, Calvo EL, Ortiz EM, Vasseur S, Keim V, Morisset J, Iovanna JL (1997) Cloning and expression of the rat p8 cDNA, a new gene activated in pancreas during the acute phase of pancreatitis, pancreatic development, and regeneration, and which promotes cellular growth. J Biol Chem 272:32360–32369.CrossRefPubMedGoogle Scholar
- Mechoulam R, Spatz M, Shohami E (2002) Endocannabinoids and neuroprotection. Sci STKE 2002:RE5.Google Scholar
- Melck D, De Petrocellis L, Orlando P, Bisogno T, Laezza C, Bifulco M, Di Marzo V (2000) Suppression of nerve growth factor Trk receptors and prolactin receptors by endocannabinoids leads to inhibition of human breast and prostate cancer cell proliferation. Endocrinology 141:118–126.CrossRefPubMedGoogle Scholar
- Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996.CrossRefPubMedGoogle Scholar