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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 CD11b, CD14, and CD38 expression. Flow cytometric analysis of expression of CD11b and CD14 at 0, 48, and 72 hr after treatment with ZW2-1, respectively, and expression of CD38 at 0, 6, and 12 hr after treatment with ZW2-1. To measure the percent positive signal, control group was set to exclude about 95% of the live cell population peak. All experiments are presented as mean ± SD of three independent experiments performed in replicates.
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fig5: Effects of ZW2-1 on CD11b, CD14, and CD38 expression. Flow cytometric analysis of expression of CD11b and CD14 at 0, 48, and 72 hr after treatment with ZW2-1, respectively, and expression of CD38 at 0, 6, and 12 hr after treatment with ZW2-1. To measure the percent positive signal, control group was set to exclude about 95% of the live cell population peak. All experiments are presented as mean ± SD of three independent experiments performed in replicates.

Mentions: Since CD38 is one of the earliest markers of progressive differentiation, we investigated the CD38 expression after 0, 6, and 12 hr incubation with ZW2-1. FACS analysis revealed that ZW2-1 treatment significantly increased CD38 expression both in HL-60 (from 5.13% to 12.5% and 44.1%) and in NB4 (from 7.39% to 23.2% and 34.4%) cell (Figure 5).


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 CD11b, CD14, and CD38 expression. Flow cytometric analysis of expression of CD11b and CD14 at 0, 48, and 72 hr after treatment with ZW2-1, respectively, and expression of CD38 at 0, 6, and 12 hr after treatment with ZW2-1. To measure the percent positive signal, control group was set to exclude about 95% of the live cell population peak. All experiments are presented as mean ± SD of three independent experiments performed in replicates.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4663760&req=5

fig5: Effects of ZW2-1 on CD11b, CD14, and CD38 expression. Flow cytometric analysis of expression of CD11b and CD14 at 0, 48, and 72 hr after treatment with ZW2-1, respectively, and expression of CD38 at 0, 6, and 12 hr after treatment with ZW2-1. To measure the percent positive signal, control group was set to exclude about 95% of the live cell population peak. All experiments are presented as mean ± SD of three independent experiments performed in replicates.
Mentions: Since CD38 is one of the earliest markers of progressive differentiation, we investigated the CD38 expression after 0, 6, and 12 hr incubation with ZW2-1. FACS analysis revealed that ZW2-1 treatment significantly increased CD38 expression both in HL-60 (from 5.13% to 12.5% and 44.1%) and in NB4 (from 7.39% to 23.2% and 34.4%) cell (Figure 5).

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