Please use this identifier to cite or link to this item:
Title: Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition.
Authors: Caffarel, María M
Andradas, Clara
Mira, Emilia
Pérez-Gómez, Eduardo
Cerutti, Camilla
Moreno-Bueno, Gema
Flores, Juana M
García-Real, Isabel
Palacios, José
Mañes, Santos
Guzmán, Manuel
Sánchez, Cristina
metadata.dc.contributor.authoraffiliation: [Caffarel,MM; Andradas,C; Pérez-Gómez,E; Cerutti,C; Guzmán,M; Sánchez,C] Dept. Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain. [Mira,E; Mañes,S] Dept. Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain. [Moreno-Bueno,G] Dept. Biochemistry, School of Medicine, Universidad Autónoma-Instituto de Investigaciones Biomédicas "Alberto Sols", IdiPaz, Madrid, Spain. [Flores,JM; García-Real,I] Dept. Animal Surgery and Medicine, School of Veterinary, Complutense University, Madrid, Spain. [Palacios,J] Servicio de Anatomía Patológica, Hospital Virgen del Rocío, Seville, Spain. [Caffarel,MM] Dept. Pathology, University of Cambridge, United Kingdom; CC, Dept. Life Sciences, The Open University, Milton Keynes, UK.
Keywords: Cannabinoides;Progresión de la Enfermedad;Regulación hacia Abajo;Femenino;Humanos;Metástasis de la Neoplasia;Inhibidores de las Proteína Quinasas;Proteínas Proto-Oncogénicas c-akt;Receptor Cannabinoide CB2;Receptor erbB-2;Neoplasias de la Mama
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoids
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Down-Regulation
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::Proto-Oncogene Proteins c-akt
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB2
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, erbB-2
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms
Issue Date: 22-Jul-2010
Citation: Caffarel MM, Andradas C, Mira E, Pérez-Gómez E, Cerutti C, Moreno-Bueno G, et al. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Mol. Cancer. 2010; 9:196
Abstract: BACKGROUND ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors. RESULTS Our results show that both Delta9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2. CONCLUSIONS Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.
Description: Journal Article; Research Support, Non-U.S. Gov't;
metadata.dc.identifier.doi: 10.1186/1476-4598-9-196
ISSN: 1476-4598 (Online)
Appears in Collections:01- Artículos - Hospital Virgen del Rocío

Files in This Item:
File Description SizeFormat 
Caffarel_Cannabinoids.pdfArtículo publicado1,03 MBAdobe PDFView/Open
Caffarel_SupplementalFigure.pdfFiguras258,45 kBAdobe PDFView/Open

This item is protected by original copyright

This item is licensed under a Creative Commons License Creative Commons