A molecular targeting against nuclear factor-κB, as a chemotherapeutic approach for human malignant mesothelioma.
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.
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
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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).
Affiliation: Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.