Biomol Ther.  2017 Mar;25(2):202-212. 10.4062/biomolther.2016.066.

Ginsenoside Rb1 Inhibits Doxorubicin-Triggered H9C2 Cell Apoptosis via Aryl Hydrocarbon Receptor

• Zhang Y
• Wang Y
• Ma Z
• Liang Q
• Tang X
• Tan H
• Xiao C
• Gao Y

• KMID: 2375041
• DOI: http://doi.org/10.4062/biomolther.2016.066

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.

Keyword

Ginsenoside Rb1; Doxorubicin; apoptosis; AhR; CYP1A

MeSH Terms

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
Caspase 3
Caspase 8
Caspase 9
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP1A2
Cytochromes c
Doxorubicin
RNA, Messenger
RNA, Small Interfering
Receptors, Aryl Hydrocarbon