15,16-Dihydrotanshinone I (DHTS) is extracted from Salvia miltiorrhiza Bunge which is a functional food in Asia. In this study, we investigated the apoptotic effect of DHTS on the human acute myeloid leukemia (AML) type III HL-60 cell line. We found that treatment with 1.5 μg/mL DHTS increased proapoptotic Bax and Bad protein expressions and activated caspases-3, -8, and -9, thus leading to poly ADP ribose polymerase (PARP) cleavage and resulting in cell apoptosis. DHTS induced sustained c-Jun N-terminal kinase (JNK) phosphorylation and Fas ligand (FasL) expression. The anti-Fas blocking antibody reversed the DHTS-induced cell death, and the JNK-specific inhibitor, SP600125, inhibited DHTS-induced caspase-3, -8, -9, and PARP cleavage. In a xenograft nude mice model, 25 mg/kg DHTS showed a great effect in attenuating HL-60 tumor growth. Taken together, these results suggest that DHTS can induce HL-60 cell apoptosis in vitro and inhibit HL-60 cell growth in vivo; the underlying mechanisms might be mediated through activation of the JNK and FasL signal pathways.
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry
- Molecular Biology
- Computer Science Applications
Liu, J. J., Wu, H. H., Chen, T. H., Leung, W., & Liang, Y. C. (2015). 15,16-dihydrotanshinone I from the functional food Salvia miltiorrhiza exhibits anticancer activity in human HL-60 leukemia cells: In Vitro and in Vivo studies. International Journal of Molecular Sciences, 16(8), 19387-19400. https://doi.org/10.3390/ijms160819387