Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1 渭M), tanshinone IIA (0.1, 0.3, 1 and 3 渭M), or tanshinone IIA plus doxorubicin.
We found that tanshinone IIA (1 and 3 渭M) 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.
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.