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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.

Liu JJ, Wu HH, Chen TH, Leung W, Liang YC - Int J Mol Sci (2015)

Bottom 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.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 Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of 15,16-dihydrotanshinone I (DHTS) on HL-60 tumor xenografts in nude mice. HL-60 cells were subcutaneously injected between the scapulas of athymic nude mice, and the mice received an i.p. injection of 12.5 or 25 mg/kg DHTS a day for a week. (A) Body weight and (B) tumor weight were measured at the end of the experiment. Values were obtained in five samples and are presented as the mean ± S.D. *p < 0.05 versus the control.
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ijms-16-19387-f006: Effects of 15,16-dihydrotanshinone I (DHTS) on HL-60 tumor xenografts in nude mice. HL-60 cells were subcutaneously injected between the scapulas of athymic nude mice, and the mice received an i.p. injection of 12.5 or 25 mg/kg DHTS a day for a week. (A) Body weight and (B) tumor weight were measured at the end of the experiment. Values were obtained in five samples and are presented as the mean ± S.D. *p < 0.05 versus the control.

Mentions: To examine the antitumor effects of DHTS on leukemia cells in vivo, we used a nude mice xenograft model. Athymic mice bearing HL-60 tumors were treated with 12.5 and 25.0 mg/kg DHTS once a day for a week. At the end of the experiment, the body weight and tumor weight were measured. As shown in Figure 6, 25 mg/kg of DHTS significantly inhibited tumor growth by about 68.0% compared to control tumors, and body weights remained unchanged between control and drug-treated mice. These results provide further evidence that DHTS might have significant applications for cancer therapeutic purposes.


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.

Liu JJ, Wu HH, Chen TH, Leung W, Liang YC - Int J Mol Sci (2015)

Effects of 15,16-dihydrotanshinone I (DHTS) on HL-60 tumor xenografts in nude mice. HL-60 cells were subcutaneously injected between the scapulas of athymic nude mice, and the mice received an i.p. injection of 12.5 or 25 mg/kg DHTS a day for a week. (A) Body weight and (B) tumor weight were measured at the end of the experiment. Values were obtained in five samples and are presented as the mean ± S.D. *p < 0.05 versus the control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581302&req=5

ijms-16-19387-f006: Effects of 15,16-dihydrotanshinone I (DHTS) on HL-60 tumor xenografts in nude mice. HL-60 cells were subcutaneously injected between the scapulas of athymic nude mice, and the mice received an i.p. injection of 12.5 or 25 mg/kg DHTS a day for a week. (A) Body weight and (B) tumor weight were measured at the end of the experiment. Values were obtained in five samples and are presented as the mean ± S.D. *p < 0.05 versus the control.
Mentions: To examine the antitumor effects of DHTS on leukemia cells in vivo, we used a nude mice xenograft model. Athymic mice bearing HL-60 tumors were treated with 12.5 and 25.0 mg/kg DHTS once a day for a week. At the end of the experiment, the body weight and tumor weight were measured. As shown in Figure 6, 25 mg/kg of DHTS significantly inhibited tumor growth by about 68.0% compared to control tumors, and body weights remained unchanged between control and drug-treated mice. These results provide further evidence that DHTS might have significant applications for cancer therapeutic purposes.

Bottom 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.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 Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus