Ginsenoside Rb1 Inhibits Doxorubicin-Triggered H9C2 Cell Apoptosis via Aryl Hydrocarbon Receptor.
10.4062/biomolther.2016.066
- Author:
Yaxin ZHANG
1
;
Yuguang WANG
;
Zengchun MA
;
Qiande LIANG
;
Xianglin TANG
;
Hongling TAN
;
Chengrong XIAO
;
Yue GAO
Author Information
1. Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China. gaoyue@bmi.ac.cn
- Publication Type:Original Article
- Keywords:
Ginsenoside Rb1;
Doxorubicin;
apoptosis;
AhR;
CYP1A
- MeSH:
Apoptosis*;
Blotting, Western;
Cardiotoxicity;
Caspase 3;
Caspase 8;
Caspase 9;
Cytochrome P-450 CYP1A1;
Cytochrome P-450 CYP1A2;
Cytochromes c;
Doxorubicin;
Myocytes, Cardiac;
Real-Time Polymerase Chain Reaction;
Receptors, Aryl Hydrocarbon*;
RNA, Messenger;
RNA, Small Interfering;
Transfection
- From:Biomolecules & Therapeutics
2017;25(2):202-212
- CountryRepublic of Korea
- Language:English
-
Abstract:
Doxorubicin (DOX) is a highly effective chemotherapeutic agent; however, the dose-dependent cardiotoxicity associated with DOX significantly limits its clinical application. In the present study, we investigated whether Rb1 could prevent DOX-induced apoptosis in H9C2 cells via aryl hydrocarbon receptor (AhR). H9C2 cells were treated with various concentrations (−μM) of Rb1. AhR, CYP1A protein and mRNA expression were quantified with Western blot and real-time PCR analyses. We also evaluated the expression levels of caspase-3 to assess the anti-apoptotic effects of Rb1. Our results showed that Rb1 attenuated DOX-induced cardiomyocytes injury and apoptosis and reduced caspase-3 and caspase-8, but not caspase-9 activity in DOX-treated H9C2 cells. Meanwhile, pre-treatment with Rb1 decreased the expression of caspase-3 and PARP in the protein levels, with no effects on cytochrome c, Bax, and Bcl-2 in DOX-stimulated cells. Rb1 markedly decreased the CYP1A1 and CYP1A2 expression induced by DOX. Furthermore, transfection with AhR siRNA or pre-treatment with AhR antagonist CH-223191 significantly inhibited the ability of Rb1 to decrease the induction of CYP1A, as well as caspase-3 protein levels following stimulation with DOX. In conclusion, these findings indicate that AhR plays an important role in the protection of Ginsenoside Rb1 against DOX-triggered apoptosis of H9C2 cells.
