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K Umezawa
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ABSTRACT: NF-κB is a transcription factor and considered to be involved in the mechanisms of inflammation and cancer. We have designed the new NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ), which directly binds to a specific cysteine residue of Rel family proteins to inhibit their DNA-binding activity. DHMEQ showed potent anti-inflammatory and anticancer activities in many animal models. So far DHMEQ has been administered mainly into the peritoneal cavity of animals. According to the limited distribution of DHMEQ in the peritoneal cavity after intraperitoneal administration, it is likely that NF-κB in the peritoneal cells would be the main target of DHMEQ. Therefore, the inflammatory cells in the peritoneal cavity appear important for the regulation of peripheral inflammation and tumor growth in the body, and peritoneal NF-κB may be an important target for anti-inflammatory and anticancer agents in future.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2011; 65(4):252-9. · 2.24 Impact Factor
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ABSTRACT: We previously found that conophylline, an alkaloid isolated from the leaves of Ervatamia microphylla, induced beta-cell differentiation in rat pancreatic acinar carcinoma cells and in cultured fetal rat pancreatic tissue and that it also decreased the blood glucose level in streptozotocin-treated fetal rats. In the present research, we looked into the effect of conophylline on the differentiation of newborn pig pancreatic endocrine cells into insulin-secreting cells. Conophylline potentiated the differentiation of monolayer cells into insulin-producing cells in the presence of nicotinamide in 3 weeks. Next we prepared islet-like cell clusters (ICC). Cononophylline together with nicotinamide also increased the number of insulin-producing cells and the insulin content in ICC in 3-6 weeks. The ICC thus prepared were sensitive to the glucose concentration for the insulin secretion. Conophylline increased the mRNA expression of PDX-1, neurogenin3, neuroD/Beta2, and insulin in ICC. Thus, the vinca alkaloid conophylline potentiated beta-cell differentiation in porcine pancreatic endocrine-rich cells in cluster cultures. Pig pancreatic cells are practical candidate for use in transplantation therapy. Conophylline may thus be useful for the large-scale preparation of porcine insulin-producing cells for the regeneration therapy of type-1 diabetes mellitus.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 03/2010; 64(3):226-31. · 2.24 Impact Factor
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ABSTRACT: Activation of microglia has been implicated in various neurodegenerative disorders, and thus the inhibition of microglial activity may suppress these disorders. Earlier we designed and synthesized an NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) that showed anti-inflammatory and anti-tumor activities in vivo. In the present research, we studied whether DHMEQ would inhibit the activation of mouse microglial cells. DHMEQ inhibited lipopolysaccharide (LPS)-induced activation of NF-kappaB in an electrophoresis mobility shift assay. It also inhibited LPS-induced secretions of TNF-alpha and IL-6 from mouse microglial cell line 6-1 cells.
Biomedecine [?] Pharmacotherapy 08/2005; 59(6):318-22. · 2.00 Impact Factor
