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Updated: Jun 5, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Tanshinone IIA prevents doxorubicin-induced cardiomyocyte apoptosis through Akt-dependent pathway
Hong-Jye Hong1, Ju-Chi Liu, Po-Yuan Chen
1School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC.
Background:
Doxorubicin, one of the original anthracyclines, remains among the most effective anticancer drugs ever developed. Clinical use of doxorubicin is, however, greatly limited by its serious adverse cardiac effects that may ultimately lead to cardiomyopathy and heart failure. Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as 'Danshen' in traditional Chinese medicine for treating cardiovascular disorders. The objective of this study was set to evaluate the protective effect of tanshinone IIA on doxorubicin-induced cardiomyocyte apoptosis, and to explore its intracellular mechanism(s).
Methods:
Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1 μM), tanshinone IIA (0.1, 0.3, 1 and 3 μM), or tanshinone IIA plus doxorubicin.
Results:
We found that tanshinone IIA (1 and 3 μM) inhibited doxorubicin-induced reactive oxygen species generation, reduced the quantity of cleaved caspase-3 and cytosol cytochrome c, and increased BcL-x(L) expression, resulting in protecting cardiomyocytes from doxorubicin-induced apoptosis. In addition, Akt phosphorylation was enhanced by tanshinone IIA treatment in cardiomyocytes. The wortmannin (100 nM), LY294002 (10 nM), and siRNA transfection for Akt significantly reduced tanshinone IIA-induced protective effect.
Conclusions:
These findings suggest that tanshinone IIA protects cardiomyocytes from doxorubicin-induced apoptosis in part through Akt-signaling pathways, which may potentially protect the heart from the severe toxicity of doxorubicin.
Insights
Tanshinone IIA protects heart cells from doxorubicin toxicity by reducing apoptosis. This effect is mediated through the Akt signaling pathway, offering potential cardioprotection against chemotherapy side effects.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- Doxorubicin is a potent anticancer drug with severe cardiotoxic side effects.
- Cardiomyopathy and heart failure are significant clinical limitations of doxorubicin treatment.
- Tanshinone IIA, from Salvia miltiorrhiza (Danshen), is used in traditional medicine for cardiovascular disorders.
Purpose of the Study:
- To evaluate the protective effect of Tanshinone IIA against doxorubicin-induced cardiomyocyte apoptosis.
- To elucidate the intracellular mechanisms underlying Tanshinone IIA's cardioprotective action.
Main Methods:
- Primary neonatal rat cardiomyocytes were cultured and treated with doxorubicin, Tanshinone IIA, or both.
- Assays were performed to measure reactive oxygen species (ROS) generation, apoptosis markers (caspase-3, cytochrome c), and anti-apoptotic protein (BcL-x(L)) expression.
- The role of the Akt signaling pathway was investigated using inhibitors (wortmannin, LY294002) and siRNA.
Main Results:
- Tanshinone IIA (1 and 3 μM) significantly inhibited doxorubicin-induced ROS generation and apoptosis.
- Tanshinone IIA reduced cleaved caspase-3 and cytosolic cytochrome c, while increasing BcL-x(L) expression.
- Tanshinone IIA enhanced Akt phosphorylation, and inhibiting Akt signaling abolished the protective effect.
Conclusions:
- Tanshinone IIA demonstrates significant cardioprotective effects against doxorubicin-induced apoptosis in cardiomyocytes.
- The protective mechanism involves the modulation of ROS, apoptosis-related proteins, and activation of the Akt signaling pathway.
- Tanshinone IIA holds potential for mitigating doxorubicin cardiotoxicity.
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