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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 a c-Jun N-terminal kinase (JNK) inhibitor on 15,16-dihydrotanshinone I (DHTS)-induced cleavages of poly ADP ribose polymerase (PAPR) and caspases in human HL-60 promyelocytic leukemia cells. Cells were pretreated with the JNK inhibitor, SP600125, for 1 h, and treated with various concentrations of DHTS for 24 h. Total cellular proteins were collected to determine protein expressions by Western blotting. SP, SP600125; CF, cleaved form; CF-casp-3, cleaved form of caspase-3; CF-casp-8, cleaved form of caspase-8; CF-casp-9, cleaved form of caspase-9. Relative intensities of CF-PARP and CF-caspases were quantified using ImageJ, normalized versus internal controls α-tubulin, and shown below the band pictures. Three independent experiments were performed and representative results are shown.
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ijms-16-19387-f005: Effects of a c-Jun N-terminal kinase (JNK) inhibitor on 15,16-dihydrotanshinone I (DHTS)-induced cleavages of poly ADP ribose polymerase (PAPR) and caspases in human HL-60 promyelocytic leukemia cells. Cells were pretreated with the JNK inhibitor, SP600125, for 1 h, and treated with various concentrations of DHTS for 24 h. Total cellular proteins were collected to determine protein expressions by Western blotting. SP, SP600125; CF, cleaved form; CF-casp-3, cleaved form of caspase-3; CF-casp-8, cleaved form of caspase-8; CF-casp-9, cleaved form of caspase-9. Relative intensities of CF-PARP and CF-caspases were quantified using ImageJ, normalized versus internal controls α-tubulin, and shown below the band pictures. Three independent experiments were performed and representative results are shown.

Mentions: To further confirm the role of JNK in apoptosis, cells were treated with the JNK inhibitor, SP600125, and expressions of cleaved caspases and PARP were detected. As shown in Figure 5, 5 μM SP600125 reversed increases in cleaved caspase-3, -8, and -9, and PARP in DHTS-treated cells. These results suggest that DHTS-induced apoptosis might be mediated through increases in FasL expression and JNK activation in HL-60 cells.


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 a c-Jun N-terminal kinase (JNK) inhibitor on 15,16-dihydrotanshinone I (DHTS)-induced cleavages of poly ADP ribose polymerase (PAPR) and caspases in human HL-60 promyelocytic leukemia cells. Cells were pretreated with the JNK inhibitor, SP600125, for 1 h, and treated with various concentrations of DHTS for 24 h. Total cellular proteins were collected to determine protein expressions by Western blotting. SP, SP600125; CF, cleaved form; CF-casp-3, cleaved form of caspase-3; CF-casp-8, cleaved form of caspase-8; CF-casp-9, cleaved form of caspase-9. Relative intensities of CF-PARP and CF-caspases were quantified using ImageJ, normalized versus internal controls α-tubulin, and shown below the band pictures. Three independent experiments were performed and representative results are shown.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-16-19387-f005: Effects of a c-Jun N-terminal kinase (JNK) inhibitor on 15,16-dihydrotanshinone I (DHTS)-induced cleavages of poly ADP ribose polymerase (PAPR) and caspases in human HL-60 promyelocytic leukemia cells. Cells were pretreated with the JNK inhibitor, SP600125, for 1 h, and treated with various concentrations of DHTS for 24 h. Total cellular proteins were collected to determine protein expressions by Western blotting. SP, SP600125; CF, cleaved form; CF-casp-3, cleaved form of caspase-3; CF-casp-8, cleaved form of caspase-8; CF-casp-9, cleaved form of caspase-9. Relative intensities of CF-PARP and CF-caspases were quantified using ImageJ, normalized versus internal controls α-tubulin, and shown below the band pictures. Three independent experiments were performed and representative results are shown.
Mentions: To further confirm the role of JNK in apoptosis, cells were treated with the JNK inhibitor, SP600125, and expressions of cleaved caspases and PARP were detected. As shown in Figure 5, 5 μM SP600125 reversed increases in cleaved caspase-3, -8, and -9, and PARP in DHTS-treated cells. These results suggest that DHTS-induced apoptosis might be mediated through increases in FasL expression and JNK activation in HL-60 cells.

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