Browsing by Author "Keiichi Koizumi"

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    Anti-angiogenic effect of curcumin, curcumin ethylenediamine derivative and curcumin ethylenediamine manganese complex
    (2004-01-01) Leena Suntornsuk; Keiichi Koizumi; Yurika Saitoh; Eliane Shizuka Nakamura; Naparat Kammasud; Opa Vajaragupta; Ikuo Saiki; Mahidol University; University of Toyama
    We investigated the anti-angiogenic effect of curcumin, curcumin ethylenediamine derivative (curcumin ED) and curcumin ethylenediamine manganese complex (curcumin EDMn) through the inhibition of the formation of tube-like structures by human umbilical vascular endothelial cells (HUVEC). Curcumin, curcumin ED, curcumin EDMn did not show cytotoxicity to HUVEC at concentrations equal and lower than 10 μM. At the concentration of 10 μM, curcumin, curcumin ED and curcumin EDMn inhibited the tube formation by approximately 94%, 40% and 65%, respectively. These results suggest that curcumin ED and curcumin EDMn might be useful as anti-angiogenic drugs in addition to their anti-lipid peroxidase and superoxide dismutase activities as described in our previous studies. © 2004, Medical and Pharmaceutical Society for WAKAN-YAKU. All rights reserved.
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    Synthesis and evaluation of 1-(substituted)-3-prop-2-ynylureas as antiangiogenic agents
    (2012-04-15) Kingkan Sanphanya; Suvara K. Wattanapitayakul; Orawin Prangsaengtong; Michiko Jo; Keiichi Koizumi; Naotoshi Shibahara; Aroonsri Priprem; Valery V. Fokin; Opa Vajragupta; Mahidol University; Srinakharinwirot University; University of Toyama; Khon Kaen University; Scripps Research Institute
    Novel urea derivatives of alkynes have been designed, synthesized, and evaluated as potential cancer therapeutics leads. The most active 1-((3-chloromethyl)phenyl)-3-prop-2-ynylurea (1) exhibited cytotoxic effect against HELA and MCF-7 cell lines with IC 50 values of 1.55 μM and 1.48 μM, respectively. Further investigation on tube formation assay in human vein umbilical cells (HUVEC) demonstrated that 1 and methyl 4-(3-(3-ethynylureido)benzyloxy) benzoate (6) possess antiangiogenic activity, with minimum effective dose of 25 nM (for 1) and 6.25 μM (for 6). The ED 50 of 1 and 6 were found to be 0.26 μM and 17.52 μM, respectively. The results from in vitro tyrosine kinase assay indicated the EGFR inhibition of 1 over other kinases (VEGFR2, FGFR1 and PDGFRβ). The cytotoxicity of 1 against EGFR overexpressing cell line A431 (IC 50 36 nM) was comparable to that of erlotinib. The binding mode of 1 from docking simulation in the EGFR active site revealed that the urea motif formed hydrogen bonding with Lys745, Thr854 and Asp855 in hydrophobic pocket of EGFR. Compound 1 is considered as a potential lead for further optimization. © 2012 Elsevier Ltd. All rights reserved.
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    Vanillin enhances TRAIL-induced apoptosis in cancer cells through inhibition of NF-κB activation
    (2010-07-01) Kriengsak Lirdprapamongkol; Hiroaki Sakurai; Shunsuke Suzuki; Keiichi Koizumi; Orawin Prangsaengtong; Amornrat Viriyaroj; Somsak Ruchirawat; Jisnuson Svasti; Ikuo Saiki; Chulabhorn Research Institute; University of Toyama; Srinakharinwirot University; Mahidol University
    Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent which selectively kills cancer cells with little effect on normal cells. However, TRAIL resistance is widely found in cancer cells. We have previously reported antimetatstatic and antiangiogenic effects of vanillin, a flavoring agent from vanilla. Here we have evaluated the sensitizing effect of vanillin on a TRAIL-resistant human cervical cancer cell line, HeLa. Materials and Methods: Cell viability after treatments was determined by the WST-1 cell counting kit. Apoptosis was demonstrated by detection of caspase-3 activation and cleavage of poly (ADP-ribose) polymerase using immunoblot analysis. Effect of treatments on TRAIL signaling pathway and nuclear factor κB (FN-κB) activation was studied using immunoblot analysis and luciferase reporter assay. Results: Pretreatment of HeLa cells with vanillin enhanced TRAIL-induced cell death through the apoptosis pathway. Vanillin pretreatment inhibited TRAIL-induced phosphorylation of p65 and transcriptional activity of NF-κB. Conclusion: Vanillin sensitizes HeLa cells to TRAIL-induced apoptosis by inhibiting NF-κB activation.