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.
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.
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, No. 250 Wuxing St., Taipei 11031, Taiwan. jjliu_96@tmu.edu.tw.
Jun-Jen
JJ
Liu
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, No. 250 Wuxing St., Taipei 11031, Taiwan. wuhh@tmu.edu.tw.
Hsueh-Hsia
HH
Wu
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, No. 250 Wuxing St., Taipei 11031, Taiwan. dennisshit@hotmail.com.
Tzu-Ho
TH
Chen
Department of Radiology and Nuclear Medicine, Yuan's General Hospital, No. 162 Cheng Kung 1st Road, Kaohsiung 80249, Taiwan. lwan@ms36.hinet.net.
Wan
W
Leung
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, No. 250 Wuxing St., Taipei 11031, Taiwan. ycliang@tmu.edu.tw.|Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, No. 252 Wuxing St., Taipei 11031, Taiwan. ycliang@tmu.edu.tw.
Yu-Chih
YC
Liang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053222:Fas Ligand Protein / Q000378:metabolism; D055951:Functional Food / Q000032:analysis; D005663:Furans; D018922:HL-60 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010616:Phenanthrenes / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D011809:Quinones; D027561:Salvia miltiorrhiza / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D053222:Fas Ligand Protein; D005663:Furans; D010616:Phenanthrenes; D011809:Quinones; C000713095:dihydrotanshinone I; D048031:JNK Mitogen-Activated Protein Kinases
15,16-dihydrotanshinone I; Fas ligand; acute myeloid leukemia; apoptosis; c-Jun N-terminal kinase