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-xL 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.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine