Polyphenol-rich fraction from Larrea divaricata and its main flavonoid Quercetin-3-Methyl Ether induce apoptosis in lymphoma cells through nitrosative stress

• Autores: Martino, Renzo; Barreiro Arcos, María Laura; Alonso, Rosario; Sülsen, Valeria; Cremaschi, Graciela A.; Anesini, Claudia
• Año de publicación: 2016
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Phytotherapy Research. 2016, 30(7)
• Materia: APOPTOSIS; LARREA DIVARICATA; LINFOMA DE CELULAS T; ETIL ACETATO; OXIDO NITRICO; POLIFENOLES; QUERCETINA; LINFOMAS
• Institución: Pontificia Universidad Católica Argentina

Fil: Martino, Renzo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina
Fil: Martino, Renzo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Barreiro Arcos, María Laura. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Barreiro Arcos, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Alonso, Rosario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina
Fil: Alonso, Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sülsen, Valeria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina
Fil: Sülsen, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cremaschi, Graciela A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina
Fil: Cremaschi, Graciela A. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Anesini, Claudia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina
Fil: Anesini, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Abstract: Larrea divaricata is a plant with antiproliferative principles. We have previously identified the flavonoid quercetin-3-methyl ether (Q-3-ME) in an ethyl acetate fraction (EA). Both the extract and Q-3-ME were found to be effective against the EL-4 T lymphoma cell line. However, the mechanism underlying the inhibition of tumor cell proliferation remains to be elucidated. In this work, we analyzed the role of nitric oxide (NO) in the induction of apoptosis mediated by Q-3-ME and EA. Both treatments were able to induce apoptosis in a concentration-dependent and time-dependent manner. The western blot analysis revealed a sequential activation of caspases-9 and 3, followed by poly-(ADP-ribose)-polymerase cleavage. EA and Q-3-ME lowered the mitochondrial membrane potential, showing the activation of the intrinsic pathway of apoptosis. Q-3-ME and EA increased NO production and inducible NO synthase expression in tumor cells. The involvement of NO in cell death was confirmed by the nitric oxide synthases inhibitor L-NAME. In addition, EA and Q-3-ME induced a cell cycle arrest in G0/G1 phase. These drugs did not affect normal cell viability. This data suggested that EA and Q-3-ME induce an increase in NO production that would lead to the cell cycle arrest and the activation of the intrinsic pathway of apoptosis. Copyright © 2016 John Wiley & Sons, Ltd.