Polyphenol-Rich Fraction from Larrea divaricata and its Main Flavonoid Quercetin-3-Methyl Ether Induce Apoptosis in Lymphoma Cells Through Nitrosative Stress.
Phytother Res
; 30(7): 1128-36, 2016 Jul.
Article
en En
| MEDLINE
| ID: mdl-27038396
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Quercetina
/
Extractos Vegetales
/
Apoptosis
/
Larrea
/
Polifenoles
/
Linfoma
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Phytother Res
Asunto de la revista:
TERAPIAS COMPLEMENTARES
Año:
2016
Tipo del documento:
Article
País de afiliación:
Argentina