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Developing a Novel Indolocarbazole as Histone Deacetylases Inhibitor against Leukemia Cell Lines.

Wang W, Lv M, Zhao X, Zhang J - J Anal Methods Chem (2015)

Bottom Line: ZW2-1 performed anti-population growth effect which was in a concentration-dependent manner (2-12 μM) by inducing both apoptosis and autophagy in cells.At relatively high concentration (8 μM), ZW2-1 significantly decreased intracellular histone deacetylase 1 level which was also observed.All the results indicated that ZW2-1 could be a novel antileukemia lead capable of simultaneously inducing apoptosis, autophagy, and differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Blood Biopharmaceuticals and Viral Detection, Institute of Transfusion Medicine, The Academy of Military Medical Sciences, Beijing 100850, China.

ABSTRACT
A novel indolocarbazole (named as ZW2-1) possessing HDAC inhibition activity was synthesized and evaluated against human leukemia cell lines HL-60 and NB4. ZW2-1 performed anti-population growth effect which was in a concentration-dependent manner (2-12 μM) by inducing both apoptosis and autophagy in cells. The compound also caused differentiation of HL-60 and NB4 cells as shown by increasing expression of CD11b, CD14, and CD38 at moderate concentration (4 μM). At relatively high concentration (8 μM), ZW2-1 significantly decreased intracellular histone deacetylase 1 level which was also observed. All the results indicated that ZW2-1 could be a novel antileukemia lead capable of simultaneously inducing apoptosis, autophagy, and differentiation.

No MeSH data available.


Related in: MedlinePlus

Effects of ZW2-1 on histone acetylation 1 in HL-60 cells. Colorimetric sandwich ELISA assay was used to detect the HDAC1 level in HL-60 and NB4 cells after treatment with ZW2-1 for 0, 24, 48, and 72 h. (a) Standard curve for samples of HL-60 cells. (b) HDAC1 concentrations of HL-60 cells treated with ZW2-1. (c) Standard curve for samples of NB4 cells. (d) HDAC1 concentrations of NB4 cells treated with ZW2-1. Data represents the means of three repeats ± SD.
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fig6: Effects of ZW2-1 on histone acetylation 1 in HL-60 cells. Colorimetric sandwich ELISA assay was used to detect the HDAC1 level in HL-60 and NB4 cells after treatment with ZW2-1 for 0, 24, 48, and 72 h. (a) Standard curve for samples of HL-60 cells. (b) HDAC1 concentrations of HL-60 cells treated with ZW2-1. (c) Standard curve for samples of NB4 cells. (d) HDAC1 concentrations of NB4 cells treated with ZW2-1. Data represents the means of three repeats ± SD.

Mentions: To determine the HDAC1 inhibition activity of ZW2-1, we tested the HDAC1 levels in HL-60 and NB4 cells before and after treatment with ZW2-1 by ELISA (Figure 6). HL-60 and NB4 cells were treated with 8 μM ZW2-1 and HDAC1 enzymatic activities were measured after for 24, 48, and 72 hours. As the results showed, intracellular concentration of HDAC was reduced by 36.9% (P < 0.01), 70% (P < 0.01), and 90.8% (P < 0.01) in HL-60 cells and by 20.6% (P < 0.05), 47.3% (P < 0.01), and 68.6% (P < 0.01) in NB4 cells following exposure to 8 μM ZW2-1 for 24, 48, and 72 hours, respectively.


Developing a Novel Indolocarbazole as Histone Deacetylases Inhibitor against Leukemia Cell Lines.

Wang W, Lv M, Zhao X, Zhang J - J Anal Methods Chem (2015)

Effects of ZW2-1 on histone acetylation 1 in HL-60 cells. Colorimetric sandwich ELISA assay was used to detect the HDAC1 level in HL-60 and NB4 cells after treatment with ZW2-1 for 0, 24, 48, and 72 h. (a) Standard curve for samples of HL-60 cells. (b) HDAC1 concentrations of HL-60 cells treated with ZW2-1. (c) Standard curve for samples of NB4 cells. (d) HDAC1 concentrations of NB4 cells treated with ZW2-1. Data represents the means of three repeats ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4663760&req=5

fig6: Effects of ZW2-1 on histone acetylation 1 in HL-60 cells. Colorimetric sandwich ELISA assay was used to detect the HDAC1 level in HL-60 and NB4 cells after treatment with ZW2-1 for 0, 24, 48, and 72 h. (a) Standard curve for samples of HL-60 cells. (b) HDAC1 concentrations of HL-60 cells treated with ZW2-1. (c) Standard curve for samples of NB4 cells. (d) HDAC1 concentrations of NB4 cells treated with ZW2-1. Data represents the means of three repeats ± SD.
Mentions: To determine the HDAC1 inhibition activity of ZW2-1, we tested the HDAC1 levels in HL-60 and NB4 cells before and after treatment with ZW2-1 by ELISA (Figure 6). HL-60 and NB4 cells were treated with 8 μM ZW2-1 and HDAC1 enzymatic activities were measured after for 24, 48, and 72 hours. As the results showed, intracellular concentration of HDAC was reduced by 36.9% (P < 0.01), 70% (P < 0.01), and 90.8% (P < 0.01) in HL-60 cells and by 20.6% (P < 0.05), 47.3% (P < 0.01), and 68.6% (P < 0.01) in NB4 cells following exposure to 8 μM ZW2-1 for 24, 48, and 72 hours, respectively.

Bottom Line: ZW2-1 performed anti-population growth effect which was in a concentration-dependent manner (2-12 μM) by inducing both apoptosis and autophagy in cells.At relatively high concentration (8 μM), ZW2-1 significantly decreased intracellular histone deacetylase 1 level which was also observed.All the results indicated that ZW2-1 could be a novel antileukemia lead capable of simultaneously inducing apoptosis, autophagy, and differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Blood Biopharmaceuticals and Viral Detection, Institute of Transfusion Medicine, The Academy of Military Medical Sciences, Beijing 100850, China.

ABSTRACT
A novel indolocarbazole (named as ZW2-1) possessing HDAC inhibition activity was synthesized and evaluated against human leukemia cell lines HL-60 and NB4. ZW2-1 performed anti-population growth effect which was in a concentration-dependent manner (2-12 μM) by inducing both apoptosis and autophagy in cells. The compound also caused differentiation of HL-60 and NB4 cells as shown by increasing expression of CD11b, CD14, and CD38 at moderate concentration (4 μM). At relatively high concentration (8 μM), ZW2-1 significantly decreased intracellular histone deacetylase 1 level which was also observed. All the results indicated that ZW2-1 could be a novel antileukemia lead capable of simultaneously inducing apoptosis, autophagy, and differentiation.

No MeSH data available.


Related in: MedlinePlus