RT Journal Article
T1 Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition.
A1 Caffarel, María M
A1 Andradas, Clara
A1 Mira, Emilia
A1 Pérez-Gómez, Eduardo
A1 Cerutti, Camilla
A1 Moreno-Bueno, Gema
A1 Flores, Juana M
A1 García-Real, Isabel
A1 Palacios, José
A1 Mañes, Santos
A1 Guzmán, Manuel
A1 Sánchez, Cristina
K1 Cannabinoides
K1 Progresión de la Enfermedad
K1 Regulación hacia Abajo
K1 Femenino
K1 Humanos
K1 Metástasis de la Neoplasia
K1 Inhibidores de las Proteína Quinasas
K1 Proteínas Proto-Oncogénicas c-akt
K1 Receptor Cannabinoide CB2
K1 Receptor erbB-2
K1 Neoplasias de la Mama
AB BACKGROUNDErbB2-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.RESULTSOur 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.CONCLUSIONSTaken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.
PB BIOMED CENTRAL LTD
YR 2010
FD 2010-07-22
LK http://hdl.handle.net/10668/1668
UL http://hdl.handle.net/10668/1668
LA en
NO 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
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 17, 2025