期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 16, 期 8, 页码 19387-19400出版社
MDPI AG
DOI: 10.3390/ijms160819387
关键词
15,16-dihydrotanshinone I; acute myeloid leukemia; c-Jun N-terminal kinase; Fas ligand; apoptosis
资金
- National Science Council of the Republic of China [NSC101-2320-B-038-017-MY3]
- Yuan's General Hospital [103YGH-TMU-02-2]
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 g/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.
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