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

Jun Jen Liu, Hsueh Hsia Wu, Tzu Ho Chen, Wan Leung, Yu Chih Liang

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)19387-19400
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume16
Issue number8
DOIs
Publication statusPublished - Aug 17 2015

Keywords

  • 15, 16-dihydrotanshinone I
  • Acute myeloid leukemia
  • Apoptosis
  • C-Jun N-terminal kinase
  • Fas ligand

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications

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