Doxorubicin-induced normal breast epithelial cellular aging and its related breast cancer growth through mitochondrial autophagy and oxidative stress mitigated by ginsenoside Rh2.
Phytother Res
; 34(7): 1659-1669, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-32100342
ABSTRACT
Clinical dose of doxorubicin (100 nM) induced cellular senescence and various secretory phenotypes in breast cancer and normal epithelial cells. Herein, we reported the detailed mechanism underlying ginsenoside Rh2-mediated NF-κB inhibition, and mitophagy promotion were evaluated by antibody array assay, western blotting analysis, and immunocytostaining. Ginsenoside Rh2 suppressed the protein levels of TRAF6, p62, phosphorylated IKK, and IκB, which consequently inactivated NF-κB activity. Rh2-mediated secretory phenotype was delineated by the suppressed IL-8 secretion. Senescent epithelial cells showed increased level of reactive oxygen species (ROS), which was significantly abrogated by Rh2, with upregulation on SIRT 3 and SIRT 5 and subsequent increase in SOD1 and SOD2. Rh2 remarkably favored mitophagy by the increased expressions of PINK1 and Parkin and decreased level of PGC-1α. A decreased secretion of IL-8 challenged by mitophagy inhibitor Mdivi-1 with an NF-κB luciferase system was confirmed. Importantly, secretory senescent epithelial cells promoted the breast cancer (MCF-7) proliferation while decreased the survival of normal epithelial cells demonstrated by co-culture system, which was remarkably alleviated by ginsenoside Rh2 treatment. These data included ginsenoside Rh2 regulated ROS and mitochondrial autophagy, which were in large part attributed to secretory phenotype of senescent breast epithelial cells induced by doxorubicin. These findings also suggested that ginsenoside Rh2 is a potential treatment candidate for the attenuation of aging related disease.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Medicamentos de Ervas Chinesas
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Doxorrubicina
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Ginsenosídeos
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Mitocôndrias
Limite:
Female
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Humans
Idioma:
En
Revista:
Phytother Res
Ano de publicação:
2020
Tipo de documento:
Article