Título
Cholesterol overload in the liver aggravates oxidative stress-mediated DNA damage and accelerates hepatocarcinogenesis
Autor
GLORIA CRISTINA ENRIQUEZ CORTINA
OSCAR BELLO MONROY
DIANA PATRICIA ROSALES CRUZ
VERONICA SOUZA ARROYO
ROXANA URI MIRANDA LABRA
RAFAEL TOLEDO PEREZ
ARMANDO LUNA LOPEZ
ARTURO SIMONI NIEVES
Rogelio Hernández-Pando
MARIA CONCEPCION GUTIERREZ RUIZ
Diego Francesco CALVISI
Jens Marquardt
LETICIA BUCIO ORTIZ
LUIS ENRIQUE GOMEZ QUIROZ
Nivel de Acceso
Acceso Abierto
Materias
MEDICINA Y CIENCIAS DE LA SALUD - (CTI) BIOLOGÍA Y QUÍMICA - (CTI) Colesterol - ([Oncotarget (1949-2553) vol. 8 (2017)]) Estrés oxidativo - ([Oncotarget (1949-2553) vol. 8 (2017)]) Daño de ADN - ([Oncotarget (1949-2553) vol. 8 (2017)]) Carcinogenesis - ([Oncotarget (1949-2553) vol. 8 (2017)]) Hígado - ([Oncotarget (1949-2553) vol. 8 (2017)]) Cáncer - ([Oncotarget (1949-2553) vol. 8 (2017)]) Cholesterol - ([Oncotarget (1949-2553) vol. 8 (2017)]) Oxidative Stress - ([Oncotarget (1949-2553) vol. 8 (2017)]) DNA Damage - ([Oncotarget (1949-2553) vol. 8 (2017)])
Resumen o descripción
Primary liver cancers represent the second leading cause of cancer-related deaths worldwide. Diverse etiological factors include chronic viral hepatitis, aflatoxin and alcohol exposure as well as aberrant liver lipid overload. Cholesterol has been identified as a key inducer of metabolic impairment, oxidative stress and promoter of cellular dysfunction. The aim of this work was to address the oxidative stress-mediated DNA damage induced by cholesterol overload, and its role in the development of hepatocellular carcinoma.
C57BL/6 male mice were fed with a high cholesterol diet, followed by a single dose of N-diethylnitrosamine (DEN, 10 μg/g, ip). Reactive oxygen species generation, DNA oxidation, antioxidant and DNA repair proteins were analyzed at different time points. Diet-induced cholesterol overload caused enhanced oxidative DNA damage in the liver and was associated with a decrease in key DNA repair genes as early as 7 days. Interestingly, we found a cell survival response, induced by cholesterol, judged by a decrement in Bax to Bcl2 ratio. Importantly, N-acetyl-cysteine supplementation significantly prevented DNA oxidation damage. Furthermore, at 8 months after DEN administration, tumor growth was significantly enhanced in mice under cholesterol diet in comparison to control animals. Together, these results suggest that cholesterol overload exerts an oxidative stress-mediated effects and promotes the development of liver cancer.
Editor
Impact Journals
Fecha de publicación
2017
Tipo de publicación
Artículo
Recurso de información
Formato
Adobe PDF
application/pdf
Fuente
Oncotarget (1949-2553) vol. 8 (2017)
Idioma
Inglés
Relación
http://www.oncotarget.com/index.php?journal=oncotarget
&
page=article
&
op=view
&
path%5b%5d=22024
&
path%5b%5d=69807#R10
Repositorio Orígen
INSTITUTO NACIONAL DE GERIATRIA
Descargas
0