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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

TEM images of HL-60 cells treated with ZW2-1 and western blots analysis of autophagy marker protein LC3. (a) Control group. (b, d) Cells were exposed to ZW2-1. (c, e) The magnification of selected area. (f) Effect of ZW2-1 on the LC3-I/LC3-II conversion.
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fig4: TEM images of HL-60 cells treated with ZW2-1 and western blots analysis of autophagy marker protein LC3. (a) Control group. (b, d) Cells were exposed to ZW2-1. (c, e) The magnification of selected area. (f) Effect of ZW2-1 on the LC3-I/LC3-II conversion.

Mentions: In order to observe the activation of autophagy of ZW2-1 (8 μM, 48 hr) treated HL-60 cells, the TEM ultrastructural analysis was performed. The autophagic ultrastructural features are shown in Figure 4. The typical autophagic vacuoles (Figure 4(e)), three obviously larger autophagic vacuoles, contained partially degraded cytoplasmic materials (Figure 4(c)), and the control cells (Figure 4(a)) are compared. The ZW2-1 induced autophagy was further verified by assessing the LC3-I/LC3-II conversion. The western blot analysis showed that the LC3-II/LC3-I ratio was significantly elevated, indicating that the autophagic activity was enhanced by ZW2-1 (Figure 4(f)), and ZW2-1 induces autophagy as well as apoptosis.


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)

TEM images of HL-60 cells treated with ZW2-1 and western blots analysis of autophagy marker protein LC3. (a) Control group. (b, d) Cells were exposed to ZW2-1. (c, e) The magnification of selected area. (f) Effect of ZW2-1 on the LC3-I/LC3-II conversion.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4663760&req=5

fig4: TEM images of HL-60 cells treated with ZW2-1 and western blots analysis of autophagy marker protein LC3. (a) Control group. (b, d) Cells were exposed to ZW2-1. (c, e) The magnification of selected area. (f) Effect of ZW2-1 on the LC3-I/LC3-II conversion.
Mentions: In order to observe the activation of autophagy of ZW2-1 (8 μM, 48 hr) treated HL-60 cells, the TEM ultrastructural analysis was performed. The autophagic ultrastructural features are shown in Figure 4. The typical autophagic vacuoles (Figure 4(e)), three obviously larger autophagic vacuoles, contained partially degraded cytoplasmic materials (Figure 4(c)), and the control cells (Figure 4(a)) are compared. The ZW2-1 induced autophagy was further verified by assessing the LC3-I/LC3-II conversion. The western blot analysis showed that the LC3-II/LC3-I ratio was significantly elevated, indicating that the autophagic activity was enhanced by ZW2-1 (Figure 4(f)), and ZW2-1 induces autophagy as well as apoptosis.

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