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Int. J. Mol. Sci. 2015, 16(8), 19387-19400; doi:10.3390/ijms160819387

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

1
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, No. 250 Wuxing St., Taipei 11031, Taiwan
2
Department of Radiology and Nuclear Medicine, Yuan’s General Hospital, No. 162 Cheng Kung 1st Road, Kaohsiung 80249, Taiwan
3
Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, No. 252 Wuxing St., Taipei 11031, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editor: Sanjay K. Srivastava
Received: 31 March 2015 / Revised: 3 August 2015 / Accepted: 6 August 2015 / Published: 17 August 2015
(This article belongs to the Special Issue Bioactive Phytochemicals in Functional Foods for Cancer Prevention)
View Full-Text   |   Download PDF [2598 KB, uploaded 17 August 2015]   |  

Abstract

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. View Full-Text
Keywords: 15,16-dihydrotanshinone I; acute myeloid leukemia; c-Jun N-terminal kinase; Fas ligand; apoptosis 15,16-dihydrotanshinone I; acute myeloid leukemia; c-Jun N-terminal kinase; Fas ligand; apoptosis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Liu, J.-J.; Wu, H.-H.; Chen, T.-H.; Leung, W.; Liang, Y.-C. 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. Int. J. Mol. Sci. 2015, 16, 19387-19400.

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