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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 mitochondria membrane electrochemical potential of HL-60 cells. HL-60 cells were stained with JC-1 dye (P2: aggregated JC-1, red fluorescence (PE); P3: monomeric JC-1, green fluorescence (FITC)) which was measured by flow cytometry. The value represents the average percentage of cells in each gate (n = 3).
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fig3: Effects of ZW2-1 on mitochondria membrane electrochemical potential of HL-60 cells. HL-60 cells were stained with JC-1 dye (P2: aggregated JC-1, red fluorescence (PE); P3: monomeric JC-1, green fluorescence (FITC)) which was measured by flow cytometry. The value represents the average percentage of cells in each gate (n = 3).

Mentions: Loss of the mitochondrial membrane potential (MMP) is a hallmark of intrinsic apoptosis, because it is associated with the release of proapoptotic proteins into the cytosol. To assess mitochondrial membrane potential, HL-60 and NB4 cells were incubated with ZW2-1 for 48 hr, and cells were then incubated with JC-1 and were analyzed by both red and green fluorescence emissions by flow cytometry. After treatment with 8 μM ZW2-1 for 48 hr, the proportion of the cells having mitochondrial membrane dysfunction increased from 2.0% to 55.0% in HL-60 cells and from 10.7% to 62.1% in NB4 cells, suggesting that ZW2-1 treatment resulted in a loss of mitochondrial membrane potential in AML cells (Figure 3).


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 mitochondria membrane electrochemical potential of HL-60 cells. HL-60 cells were stained with JC-1 dye (P2: aggregated JC-1, red fluorescence (PE); P3: monomeric JC-1, green fluorescence (FITC)) which was measured by flow cytometry. The value represents the average percentage of cells in each gate (n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4663760&req=5

fig3: Effects of ZW2-1 on mitochondria membrane electrochemical potential of HL-60 cells. HL-60 cells were stained with JC-1 dye (P2: aggregated JC-1, red fluorescence (PE); P3: monomeric JC-1, green fluorescence (FITC)) which was measured by flow cytometry. The value represents the average percentage of cells in each gate (n = 3).
Mentions: Loss of the mitochondrial membrane potential (MMP) is a hallmark of intrinsic apoptosis, because it is associated with the release of proapoptotic proteins into the cytosol. To assess mitochondrial membrane potential, HL-60 and NB4 cells were incubated with ZW2-1 for 48 hr, and cells were then incubated with JC-1 and were analyzed by both red and green fluorescence emissions by flow cytometry. After treatment with 8 μM ZW2-1 for 48 hr, the proportion of the cells having mitochondrial membrane dysfunction increased from 2.0% to 55.0% in HL-60 cells and from 10.7% to 62.1% in NB4 cells, suggesting that ZW2-1 treatment resulted in a loss of mitochondrial membrane potential in AML cells (Figure 3).

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