Ginsenoside Rb1 Inhibits Doxorubicin-Triggered H9C2 Cell ApoptosisviaAryl Hydrocarbon Receptor.
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 cellsviaaryl 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.
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Yaxin
Y
Zhang
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Yuguang
Y
Wang
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Zengchun
Z
Ma
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Qiande
Q
Liang
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Xianglin
X
Tang
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Hongling
H
Tan
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Chengrong
C
Xiao
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Yue
Y
Gao
AhR; CYP1A; Doxorubicin; Ginsenoside Rb1; apoptosis