RT Journal Article
T1 Cannabinoid derivatives exert a potent anti-myeloma activity both in vitro and in vivo.
A1 Barbado, M Victoria
A1 Medrano, Mayte
A1 Caballero-Velazquez, Teresa
A1 Alvarez-Laderas, Isabel
A1 Sanchez-Abarca, Luis Ignacio
A1 Garcia-Guerrero, Estefania
A1 Martin-Sanchez, Jesus
A1 Rosado, Ivan Valle
A1 Piruat, Jose Ignacio
A1 Gonzalez-Naranjo, Pedro
A1 Campillo, Nuria Eugenia
A1 Paez, Juan Antonio
A1 Perez-Simon, Jose Antonio
K1 apoptosis
K1 cannabinoids
K1 caspases
K1 ceramides
K1 multiple myeloma
AB Although hematopoietic and immune system show high levels of the cannabinoid receptor CB2, the potential effect of cannabinoids on hematologic malignancies has been poorly determined. Here we have investigated their anti-tumor effect in multiple myeloma (MM). We demonstrate that cannabinoids induce a selective apoptosis in MM cell lines and in primary plasma cells of MM patients, while sparing normal cells from healthy donors, including hematopoietic stem cells. This effect was mediated by caspase activation, mainly caspase-2, and was partially prevented by a pan-caspase inhibitor. Their pro-apoptotic effect was correlated with an increased expression of Bax and Bak, a decrease of Bcl-xL and Mcl-1, a biphasic response of Akt/PKB and an increase in the levels of ceramide in MM cells. Inhibition of ceramide synthesis partially prevented apoptosis, indicating that these sphingolipids play a key role in the pro-apoptotic effect of cannabinoids in MM cells. Remarkably, blockage of the CB2 receptor also inhibited cannabinoid-induced apoptosis. Cannabinoid derivative WIN-55 enhanced the anti-myeloma activity of dexamethasone and melphalan overcoming resistance to melphalan in vitro. Finally, administration of cannabinoid WIN-55 to plasmacytoma-bearing mice significantly suppressed tumor growth in vivo. Together, our data suggest that cannabinoids may be considered as potential therapeutic agents in the treatment of MM.
PB John Wiley & Sons, Inc.
YR 2016
FD 2016-12-14
LK http://hdl.handle.net/10668/10558
UL http://hdl.handle.net/10668/10558
LA en
NO Barbado MV, Medrano M, Caballero-Velázquez T, Álvarez-Laderas I, Sánchez-Abarca LI, García-Guerrero E, et al. Cannabinoid derivatives exert a potent anti-myeloma activity both in vitro and in vivo. Int J Cancer. 2017 Feb 1;140(3):674-685.
DS RISalud
RD Apr 8, 2025