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A molecular targeting against nuclear factor-κB, as a chemotherapeutic approach for human malignant mesothelioma.

Nishikawa S, Tanaka A, Matsuda A, Oida K, Jang H, Jung K, Amagai Y, Ahn G, Okamoto N, Ishizaka S, Matsuda H - Cancer Med (2014)

Bottom Line: IMD-0354 reduced cyclin D3 in both epithelial tissue type NCI-H28 and sarcomatoid tissue type NCI-H2052.In a sphere formation assay, IMD-0354 effectively decreased the number and diameter of MSTO-211H spheres.These results indicate that a targeted drug against NF-κB might have therapeutic efficacy in the treatment of human malignant mesothelioma.

View Article: PubMed Central - PubMed

Affiliation: Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.

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Downregulation of cell cycle regulatory and antiapoptotic proteins in mesothelioma cells upon NF-κB inhibition. (A) The expression of cyclins D1, D2, and D3 was suppressed in MSTO-211H cells and that of cyclin D3 was decreased in NCI-H28 and NCI-H2052 cells by treatment with IMD-0354 (1 μmol/L) for 24 h. In NCI-H2052 cells, Bcl-2 expression was suppressed by IMD-0354 treatment (representative of three different experiments). (B) The relative intensity of each factor was normalized to the protein expression of β-actin as an endogenous control. The intensity in the absence of IMD-0354 was scored as 1. D1, cyclin D1; D2, cyclin D2; D3, cyclin D3; E, cyclin E. Columns, means of five independent experiments; bars, ±SE. *P < 0.05 compared with medium alone. NF-κB, nuclear factor-κB.
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fig03: Downregulation of cell cycle regulatory and antiapoptotic proteins in mesothelioma cells upon NF-κB inhibition. (A) The expression of cyclins D1, D2, and D3 was suppressed in MSTO-211H cells and that of cyclin D3 was decreased in NCI-H28 and NCI-H2052 cells by treatment with IMD-0354 (1 μmol/L) for 24 h. In NCI-H2052 cells, Bcl-2 expression was suppressed by IMD-0354 treatment (representative of three different experiments). (B) The relative intensity of each factor was normalized to the protein expression of β-actin as an endogenous control. The intensity in the absence of IMD-0354 was scored as 1. D1, cyclin D1; D2, cyclin D2; D3, cyclin D3; E, cyclin E. Columns, means of five independent experiments; bars, ±SE. *P < 0.05 compared with medium alone. NF-κB, nuclear factor-κB.

Mentions: The expression of cyclins and their contribution to cell proliferation were previously demonstrated in various cell types 21,27. Since NF-κB inhibition resulted in the increase in cell numbers at the subG1/G1 phase, we examined the expression of cyclins related to the S phase entry in these mesothelioma cell lines. As shown in Figure 3A, cyclins D1, D2, D3, and E were detected in all mesothelioma cell lines, and cyclin D3 expression was significantly decreased by NF-κB suppression in all cell lines. Cyclins D1 and D2 were also significantly downregulated in MSTO-211H cells upon NF-κB inhibition. In contrast, in NCI-H2052 cells, cyclin D1 and D2 expression was increased by NF-κB suppression. Similarly, cyclin D1 was upregulated in NCI-H28 cells upon NF-κB inhibition. At the same time, we assessed the expression of the antiapoptotic protein Bcl-2 in these samples. The expression of Bcl-2 was significantly decreased upon NF-κB inhibition only in NCI-H2052 (Fig. 3).


A molecular targeting against nuclear factor-κB, as a chemotherapeutic approach for human malignant mesothelioma.

Nishikawa S, Tanaka A, Matsuda A, Oida K, Jang H, Jung K, Amagai Y, Ahn G, Okamoto N, Ishizaka S, Matsuda H - Cancer Med (2014)

Downregulation of cell cycle regulatory and antiapoptotic proteins in mesothelioma cells upon NF-κB inhibition. (A) The expression of cyclins D1, D2, and D3 was suppressed in MSTO-211H cells and that of cyclin D3 was decreased in NCI-H28 and NCI-H2052 cells by treatment with IMD-0354 (1 μmol/L) for 24 h. In NCI-H2052 cells, Bcl-2 expression was suppressed by IMD-0354 treatment (representative of three different experiments). (B) The relative intensity of each factor was normalized to the protein expression of β-actin as an endogenous control. The intensity in the absence of IMD-0354 was scored as 1. D1, cyclin D1; D2, cyclin D2; D3, cyclin D3; E, cyclin E. Columns, means of five independent experiments; bars, ±SE. *P < 0.05 compared with medium alone. NF-κB, nuclear factor-κB.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3987091&req=5

fig03: Downregulation of cell cycle regulatory and antiapoptotic proteins in mesothelioma cells upon NF-κB inhibition. (A) The expression of cyclins D1, D2, and D3 was suppressed in MSTO-211H cells and that of cyclin D3 was decreased in NCI-H28 and NCI-H2052 cells by treatment with IMD-0354 (1 μmol/L) for 24 h. In NCI-H2052 cells, Bcl-2 expression was suppressed by IMD-0354 treatment (representative of three different experiments). (B) The relative intensity of each factor was normalized to the protein expression of β-actin as an endogenous control. The intensity in the absence of IMD-0354 was scored as 1. D1, cyclin D1; D2, cyclin D2; D3, cyclin D3; E, cyclin E. Columns, means of five independent experiments; bars, ±SE. *P < 0.05 compared with medium alone. NF-κB, nuclear factor-κB.
Mentions: The expression of cyclins and their contribution to cell proliferation were previously demonstrated in various cell types 21,27. Since NF-κB inhibition resulted in the increase in cell numbers at the subG1/G1 phase, we examined the expression of cyclins related to the S phase entry in these mesothelioma cell lines. As shown in Figure 3A, cyclins D1, D2, D3, and E were detected in all mesothelioma cell lines, and cyclin D3 expression was significantly decreased by NF-κB suppression in all cell lines. Cyclins D1 and D2 were also significantly downregulated in MSTO-211H cells upon NF-κB inhibition. In contrast, in NCI-H2052 cells, cyclin D1 and D2 expression was increased by NF-κB suppression. Similarly, cyclin D1 was upregulated in NCI-H28 cells upon NF-κB inhibition. At the same time, we assessed the expression of the antiapoptotic protein Bcl-2 in these samples. The expression of Bcl-2 was significantly decreased upon NF-κB inhibition only in NCI-H2052 (Fig. 3).

Bottom Line: IMD-0354 reduced cyclin D3 in both epithelial tissue type NCI-H28 and sarcomatoid tissue type NCI-H2052.In a sphere formation assay, IMD-0354 effectively decreased the number and diameter of MSTO-211H spheres.These results indicate that a targeted drug against NF-κB might have therapeutic efficacy in the treatment of human malignant mesothelioma.

View Article: PubMed Central - PubMed

Affiliation: Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus