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Compound 331 selectively induces glioma cell death by upregulating miR-494 and downregulating CDC20.

Zhang L, Niu T, Huang Y, Zhu H, Zhong W, Lin J, Zhang Y - Sci Rep (2015)

Bottom Line: Malignant gliomas are the most common malignant tumors in the central nervous system (CNS).Up to date, the prognosis of glioma is still very poor, effective therapy with less side-effect is very necessary.These results suggest that compound 331 could be a potential drug selectively targeting glioma cells through upregulating miR-494 and downregulating CDC20.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.

ABSTRACT
Malignant gliomas are the most common malignant tumors in the central nervous system (CNS). Up to date, the prognosis of glioma is still very poor, effective therapy with less side-effect is very necessary. Herein, we identify a compound named as "331" selectively induced cell death in glioma cells but not in astrocytes. Compound 331 upregulated miR-494 and downregulated CDC20 in glioma cells but not in astrocytes. These results suggest that compound 331 could be a potential drug selectively targeting glioma cells through upregulating miR-494 and downregulating CDC20.

No MeSH data available.


Related in: MedlinePlus

Compound 331 induced apoptosis in glioma cells.(a) Flow cytometric analysis for annexin V and PI in glioma cells treated with compound 331 (20 μM, 48 h) or transfection wtih CDC20 overexpressing plasmid (24 h before treated with compound 331). Percentage of annexin V-positive and PI-negative cells (bottom right) were indicated. (b) Proteolytic activities of caspase-3/7 induced by compound 331 (20 μM, 48 h) and rescued by overexpression of CDC20 (transfected 24 h before treatment with compound 331). Data represents the mean ± S.E.M. of three independent experiments. **p < 0.01 compared with the control groups.
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f6: Compound 331 induced apoptosis in glioma cells.(a) Flow cytometric analysis for annexin V and PI in glioma cells treated with compound 331 (20 μM, 48 h) or transfection wtih CDC20 overexpressing plasmid (24 h before treated with compound 331). Percentage of annexin V-positive and PI-negative cells (bottom right) were indicated. (b) Proteolytic activities of caspase-3/7 induced by compound 331 (20 μM, 48 h) and rescued by overexpression of CDC20 (transfected 24 h before treatment with compound 331). Data represents the mean ± S.E.M. of three independent experiments. **p < 0.01 compared with the control groups.

Mentions: There has been increasing evidence suggesting that CDC20 is related to mitotic catastrophe272832. Our data demonstrated that treatment with compound 331 (20 μM, 48 h) increased the percentage of cells with multi-nuclei (Figs 5a,b,c), a character of mitotic catastrophe3334, and induced significant G2/M arrest in glioma cells. CDC20 overexpression could further rescue the increase of multi-nuclei cells and G2/M arrest in compound 331 treated glioma cells (Figs 5d,e). Furthermore, flow cytometric analysis data indicated that compound 331 (20 μM, 48 h) significantly increased the percentage of annexin V-positive and PI-negative cells (Fig. 6a). In addition, compound 331 (20 μM, 48 h) could significantly increase the enzymatic activities of caspase-3/7 in glioma cells (Fig. 6b), indicating an increase of apoptosis in treated glioma cells. Similarly, CDC20 overexpression decreased the percentage of annexin V-positive and PI-negative cells (Fig. 6a) and the enzymatic activities of caspase-3/7 (Fig. 6b) in glioma cells treated with compound 331 (20 μM, 48 h). In conclusion, compound 331 downregulated CDC20 in glioma cells and ensued in the accumulation of multi-nucleus cells, G2/M arrest, and cell apoptosis. Our data suggests that compound 331 induces mitotic catastrophe, which results in apoptosis by downregulating CDC20 in glioma cells.


Compound 331 selectively induces glioma cell death by upregulating miR-494 and downregulating CDC20.

Zhang L, Niu T, Huang Y, Zhu H, Zhong W, Lin J, Zhang Y - Sci Rep (2015)

Compound 331 induced apoptosis in glioma cells.(a) Flow cytometric analysis for annexin V and PI in glioma cells treated with compound 331 (20 μM, 48 h) or transfection wtih CDC20 overexpressing plasmid (24 h before treated with compound 331). Percentage of annexin V-positive and PI-negative cells (bottom right) were indicated. (b) Proteolytic activities of caspase-3/7 induced by compound 331 (20 μM, 48 h) and rescued by overexpression of CDC20 (transfected 24 h before treatment with compound 331). Data represents the mean ± S.E.M. of three independent experiments. **p < 0.01 compared with the control groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495416&req=5

f6: Compound 331 induced apoptosis in glioma cells.(a) Flow cytometric analysis for annexin V and PI in glioma cells treated with compound 331 (20 μM, 48 h) or transfection wtih CDC20 overexpressing plasmid (24 h before treated with compound 331). Percentage of annexin V-positive and PI-negative cells (bottom right) were indicated. (b) Proteolytic activities of caspase-3/7 induced by compound 331 (20 μM, 48 h) and rescued by overexpression of CDC20 (transfected 24 h before treatment with compound 331). Data represents the mean ± S.E.M. of three independent experiments. **p < 0.01 compared with the control groups.
Mentions: There has been increasing evidence suggesting that CDC20 is related to mitotic catastrophe272832. Our data demonstrated that treatment with compound 331 (20 μM, 48 h) increased the percentage of cells with multi-nuclei (Figs 5a,b,c), a character of mitotic catastrophe3334, and induced significant G2/M arrest in glioma cells. CDC20 overexpression could further rescue the increase of multi-nuclei cells and G2/M arrest in compound 331 treated glioma cells (Figs 5d,e). Furthermore, flow cytometric analysis data indicated that compound 331 (20 μM, 48 h) significantly increased the percentage of annexin V-positive and PI-negative cells (Fig. 6a). In addition, compound 331 (20 μM, 48 h) could significantly increase the enzymatic activities of caspase-3/7 in glioma cells (Fig. 6b), indicating an increase of apoptosis in treated glioma cells. Similarly, CDC20 overexpression decreased the percentage of annexin V-positive and PI-negative cells (Fig. 6a) and the enzymatic activities of caspase-3/7 (Fig. 6b) in glioma cells treated with compound 331 (20 μM, 48 h). In conclusion, compound 331 downregulated CDC20 in glioma cells and ensued in the accumulation of multi-nucleus cells, G2/M arrest, and cell apoptosis. Our data suggests that compound 331 induces mitotic catastrophe, which results in apoptosis by downregulating CDC20 in glioma cells.

Bottom Line: Malignant gliomas are the most common malignant tumors in the central nervous system (CNS).Up to date, the prognosis of glioma is still very poor, effective therapy with less side-effect is very necessary.These results suggest that compound 331 could be a potential drug selectively targeting glioma cells through upregulating miR-494 and downregulating CDC20.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.

ABSTRACT
Malignant gliomas are the most common malignant tumors in the central nervous system (CNS). Up to date, the prognosis of glioma is still very poor, effective therapy with less side-effect is very necessary. Herein, we identify a compound named as "331" selectively induced cell death in glioma cells but not in astrocytes. Compound 331 upregulated miR-494 and downregulated CDC20 in glioma cells but not in astrocytes. These results suggest that compound 331 could be a potential drug selectively targeting glioma cells through upregulating miR-494 and downregulating CDC20.

No MeSH data available.


Related in: MedlinePlus