Salvianolic acid A, a novel PI3K/Akt inhibitor, induces cell apoptosis and suppresses tumor growth in acute myeloid leukemia

Abstract

Salvianolic acid A (SAA), one of the main derivatives of Salvia miltiorrhiza, has been shown to possess anti-inflammatory and anti-thrombotic activities. Its role in inhibiting tumor growth, however, remains elusive. The aim of this study was to investigate the effect of SAA on acute myeloid leukemia (AML). Here, SAA showed a dose-dependent cell viability inhibition and apoptosis induction in AML cells. At the molecular level, SAA increased the expression of Bak and decreased the expression of Bcl-xL, following by PARP cleavage and caspase-3 activation. SAA also markedly attenuated Akt phosphorylation in AML cells. In a xenograft mouse model, SAA significantly suppressed the growth of AML tumors in vivo. Furthermore, SAA exhibited a more profound pro-apoptotic effect on primary AML cells than on bone marrow mononuclear cells from patients with benign diseases. Therefore, the pro-apoptotic and anti-tumor properties of SAA suggested its promising therapeutic value for AML.

Keywords:

• Salvianolic acid A
• acute myeloid leukemia
• apoptosis
• PI3K

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1399314.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No. 81400098), the K.C. Wong Magna Fund in Ningbo University, and the General Research Program of Health Bureau of Zhejiang Province (No. 2012KYB186).