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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 downregulated CDC20 in glioma cells.(a) Western blot analysis of Cdc20 in glioma cells and astrocytes after treatment with compound 331 (20 μM, 48 h) or transfection with CDC20 overexpressing plasmid (24 h before treated with compound 331). (b) Western blot analysis of CDC20 in tumor excised from the control group and nude mice administrated by 10 mg/kg, 40 mg/kg, 80 mg/kg 331. (c) Quantification of western blotting data in a. Data represents the mean ± S.E.M. of three independent experiments. *p < 0.05, **p < 0.01. (d) Quantification of western blotting data in b. Data represents the mean ± S.E.M. of three independent experiments. *p < 0.05, **p < 0.01. (e) Quantitative RT-PCR analysis of CDC20 in glioma cells and astrocytes after treatment with compound 331 (20 μM, 48 h) or transfection with CDC20 overexpressing plasmid (24 h before treated with compound 331). Data represents the mean ± S.E.M of three independent experiments. **p < 0.01. (f) Cell viability of glioma cells after treatment with compound 331 (20 μM, 48 h) or transfection with CDC20 overexpressing plasmid (24 h before treatment with compound 331). Data represents the mean ± S.E.M. of three independent experiments. *p < 0.05, **p < 0.01. (g) Glioma cells were treated with compound 331 (20 μM, 24 h) or transfected wtih CDC20 overexpressing plasmid (24 h before treated with compound 331). The cells were stained with crystal violet (0.4 g/L). (h) Statistics of the numbers of colonies per dish. Data represents the mean ± S.E.M. of three independent experiments. **p < 0.01. (i) Representative images of CDC20 staining in the tumors excised from nude mice treated with compound 331 (10 mg/kg, 40 mg/kg and 80 mg/kg) for 21 days. Scale bar: 50 μm.
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f4: Compound 331 downregulated CDC20 in glioma cells.(a) Western blot analysis of Cdc20 in glioma cells and astrocytes after treatment with compound 331 (20 μM, 48 h) or transfection with CDC20 overexpressing plasmid (24 h before treated with compound 331). (b) Western blot analysis of CDC20 in tumor excised from the control group and nude mice administrated by 10 mg/kg, 40 mg/kg, 80 mg/kg 331. (c) Quantification of western blotting data in a. Data represents the mean ± S.E.M. of three independent experiments. *p < 0.05, **p < 0.01. (d) Quantification of western blotting data in b. Data represents the mean ± S.E.M. of three independent experiments. *p < 0.05, **p < 0.01. (e) Quantitative RT-PCR analysis of CDC20 in glioma cells and astrocytes after treatment with compound 331 (20 μM, 48 h) or transfection with CDC20 overexpressing plasmid (24 h before treated with compound 331). Data represents the mean ± S.E.M of three independent experiments. **p < 0.01. (f) Cell viability of glioma cells after treatment with compound 331 (20 μM, 48 h) or transfection with CDC20 overexpressing plasmid (24 h before treatment with compound 331). Data represents the mean ± S.E.M. of three independent experiments. *p < 0.05, **p < 0.01. (g) Glioma cells were treated with compound 331 (20 μM, 24 h) or transfected wtih CDC20 overexpressing plasmid (24 h before treated with compound 331). The cells were stained with crystal violet (0.4 g/L). (h) Statistics of the numbers of colonies per dish. Data represents the mean ± S.E.M. of three independent experiments. **p < 0.01. (i) Representative images of CDC20 staining in the tumors excised from nude mice treated with compound 331 (10 mg/kg, 40 mg/kg and 80 mg/kg) for 21 days. Scale bar: 50 μm.

Mentions: Western blot and RT-PCR data confirmed that CDC20 was downregulated by compound 331 treatment both in vitro in cultured glioma cells (20 μM, 48 h, Figs 4a,c,e) and in vivo in nude mice (Figs 4b,d). In astrocytes, CDC20 levels did not significantly alter at the mRNA level nor protein level after treated with compound 331 (20 μM, 48 h) (Figs 4a,c,e). Overexpression of CDC20 could significantly increase cell viability of glioma cells treated with compound 331 (20 μM, 48 h) (Fig. 4f). In addition, overexpression of CDC20 could also significantly rescue the glioma cells ability to form colonies (Figs 4g,h). At the same time, CDC20 was also significantly downregulated in the tumor xenografts from the nude mice treated with 331 (10 mg/kg, 40 mg/kg, 80 mg/kg) (Fig. 4i).


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 downregulated CDC20 in glioma cells.(a) Western blot analysis of Cdc20 in glioma cells and astrocytes after treatment with compound 331 (20 μM, 48 h) or transfection with CDC20 overexpressing plasmid (24 h before treated with compound 331). (b) Western blot analysis of CDC20 in tumor excised from the control group and nude mice administrated by 10 mg/kg, 40 mg/kg, 80 mg/kg 331. (c) Quantification of western blotting data in a. Data represents the mean ± S.E.M. of three independent experiments. *p < 0.05, **p < 0.01. (d) Quantification of western blotting data in b. Data represents the mean ± S.E.M. of three independent experiments. *p < 0.05, **p < 0.01. (e) Quantitative RT-PCR analysis of CDC20 in glioma cells and astrocytes after treatment with compound 331 (20 μM, 48 h) or transfection with CDC20 overexpressing plasmid (24 h before treated with compound 331). Data represents the mean ± S.E.M of three independent experiments. **p < 0.01. (f) Cell viability of glioma cells after treatment with compound 331 (20 μM, 48 h) or transfection with CDC20 overexpressing plasmid (24 h before treatment with compound 331). Data represents the mean ± S.E.M. of three independent experiments. *p < 0.05, **p < 0.01. (g) Glioma cells were treated with compound 331 (20 μM, 24 h) or transfected wtih CDC20 overexpressing plasmid (24 h before treated with compound 331). The cells were stained with crystal violet (0.4 g/L). (h) Statistics of the numbers of colonies per dish. Data represents the mean ± S.E.M. of three independent experiments. **p < 0.01. (i) Representative images of CDC20 staining in the tumors excised from nude mice treated with compound 331 (10 mg/kg, 40 mg/kg and 80 mg/kg) for 21 days. Scale bar: 50 μm.
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f4: Compound 331 downregulated CDC20 in glioma cells.(a) Western blot analysis of Cdc20 in glioma cells and astrocytes after treatment with compound 331 (20 μM, 48 h) or transfection with CDC20 overexpressing plasmid (24 h before treated with compound 331). (b) Western blot analysis of CDC20 in tumor excised from the control group and nude mice administrated by 10 mg/kg, 40 mg/kg, 80 mg/kg 331. (c) Quantification of western blotting data in a. Data represents the mean ± S.E.M. of three independent experiments. *p < 0.05, **p < 0.01. (d) Quantification of western blotting data in b. Data represents the mean ± S.E.M. of three independent experiments. *p < 0.05, **p < 0.01. (e) Quantitative RT-PCR analysis of CDC20 in glioma cells and astrocytes after treatment with compound 331 (20 μM, 48 h) or transfection with CDC20 overexpressing plasmid (24 h before treated with compound 331). Data represents the mean ± S.E.M of three independent experiments. **p < 0.01. (f) Cell viability of glioma cells after treatment with compound 331 (20 μM, 48 h) or transfection with CDC20 overexpressing plasmid (24 h before treatment with compound 331). Data represents the mean ± S.E.M. of three independent experiments. *p < 0.05, **p < 0.01. (g) Glioma cells were treated with compound 331 (20 μM, 24 h) or transfected wtih CDC20 overexpressing plasmid (24 h before treated with compound 331). The cells were stained with crystal violet (0.4 g/L). (h) Statistics of the numbers of colonies per dish. Data represents the mean ± S.E.M. of three independent experiments. **p < 0.01. (i) Representative images of CDC20 staining in the tumors excised from nude mice treated with compound 331 (10 mg/kg, 40 mg/kg and 80 mg/kg) for 21 days. Scale bar: 50 μm.
Mentions: Western blot and RT-PCR data confirmed that CDC20 was downregulated by compound 331 treatment both in vitro in cultured glioma cells (20 μM, 48 h, Figs 4a,c,e) and in vivo in nude mice (Figs 4b,d). In astrocytes, CDC20 levels did not significantly alter at the mRNA level nor protein level after treated with compound 331 (20 μM, 48 h) (Figs 4a,c,e). Overexpression of CDC20 could significantly increase cell viability of glioma cells treated with compound 331 (20 μM, 48 h) (Fig. 4f). In addition, overexpression of CDC20 could also significantly rescue the glioma cells ability to form colonies (Figs 4g,h). At the same time, CDC20 was also significantly downregulated in the tumor xenografts from the nude mice treated with 331 (10 mg/kg, 40 mg/kg, 80 mg/kg) (Fig. 4i).

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