A Iwahori

Hoshi University, Edo, Tōkyō, Japan

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Publications (6)15.84 Total impact

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    ABSTRACT: Falconensones A and B are a new type of yellow pigment with structural similarity to retinoic acid isolated from the mycelial extract of ascomycetous fungi, Emericella falconensis or Emericella fruticulosa. In the present study we show that falconensone A alone induced apoptosis of HL60 human leukemia cells, while falconensone B, the 4'-nor-methyl derivative of falconensone A, had much lower activity. The synthetic derivatives of falconensone A, falconensone A p-bromophenylhydrazone and falconensone A dioxime, were more potent than natural falconensone A and B as far as the induction of apoptosis was concerned. The induction of apoptosis by the falconensones correlated with their inhibition of cell growth. In addition, falconensones A and B, and falconensone A dioxime, increased the generation of intracellular reactive oxygen species, while falconensone A p-bromophenylhydrazone was inactive. These results suggest that falconensone A, falconensone A p-bromophenylhydrazone and falconensone A dioxime are potential new apoptosis-inducing agents. The enhanced generation of reactive oxygen species in cells may be involved in apoptosis induced by falconensone A and falconensone A dioxime, but not by falconensone A p-bromophenylhydrazone. It is also suggested that the methyl residue at the 4' position of the falconensone A cyclopentenone ring may be essential for the induction of apoptosis. Based on these results, falconensone A and its derivatives may be clinically useful in the treatment of some leukemias.
    Biological & Pharmaceutical Bulletin 07/2000; 23(6):748-54. · 1.85 Impact Factor
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    ABSTRACT: In order to examine the primary structure of acetoacetyl-CoA synthetase (acetoacetate-CoA ligase, EC 6.2.1.16; AA-CoA synthetase), the cDNA clone encoding this enzyme has been isolated from the cDNA library which was prepared from the liver of rat fed a diet supplemented with 4% cholestyramine and 0.4% pravastatin for 4 days. Nucleotide sequence analysis of cloned cDNA revealed that AA-CoA synthetase of rat liver contains an open reading frame of 2019 nucleotides, and the deduced amino acid sequence (672 amino acid residues) bears 25.0 and 38.9% homologies with acetyl-CoA synthetases of Saccharomyces cerevisiae and Archaeoglobus fulgidus, respectively.
    FEBS Letters 02/2000; 466(2-3):239-43. · 3.58 Impact Factor
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    ABSTRACT: In order to investigate the physiological role of acetoacetyl-CoA synthetase (acetoacetate-CoA ligase, EC 6.2.1.16), a cytosolic acetoacetate-activating enzyme, the effects of animal development on the activity and content of the enzyme were examined in rat liver. In male rats, the enzyme specific activity increased 21-fold at 4 weeks of age from that at 2 weeks of age, and then gradually decreased, while in female rats, it increased similarly to that of male rats, but further increased, reaching a maximum about 3-fold higher than that of male rats, at 6 weeks of age. The developmental patterns of the enzyme content correlated with that of the enzyme specific activity. These results indicate that changes in this enzyme activity and content during the developmental process might influence the rate of ketone body utilization for the formation of physiologically important lipidic substances in rat liver.
    Biological & Pharmaceutical Bulletin 10/1999; 22(9):981-3. · 1.85 Impact Factor
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    ABSTRACT: Mer-NF8054X is a new type of steroid whose structure has been established as 11-oxo-18, 22-cycloergosta-6, 8(14)-diene-3beta, 5beta, 9beta, 23S-tetraol (an 18, 22-cycloergostane), which has been reported to have antifungal activity against Aspergillus fumigatus. However, other biological activities are unknown. Herein, we reported that Mer-NF8054X inhibited cell growth of HL60 human leukemia cells, when used either singly or in combination with retinoic acid (RA). In addition, Mer-NF8054X alone induced differentiation and apoptosis of HL60 cells. The induction of differentiation of HL60 cells by Mer-NF8054X was synergistic in combination with RA. On the other hand, Emesterone A, an analogue of Mer-NF8054X which is missing a hydroxy residue from the third position, showed much lower activity than Mer-NF8054X on the inhibition of cell growth and the induction of cell differentiation and apoptosis. However, Emesterone B, an analogue of Emesterone A which is missing a hydroxy residue from the fifth position, showed higher activity than Emesterone A but lower activity than Mer-NF8054X when examined for the inhibition of cell growth and the induction of cell differentiation and apoptosis. These results suggested that Mer-NF8054X and its analogs may be a new type of differentiation inducing agent. The hydroxy residue at the third position or fifth position in Mer-NF8054X may be necessary, but not essential, for inhibition of growth and induction of both differentiation and apoptosis of HL60 cells. In addition, Mer-NF8054X enhanced the differentiation of HL60 cells induced by RA. Based on these results, Mer-NF8054X may have utility in the clinic in combination with RA for leukemia patients.
    Experimental Cell Research 01/1999; 245(2):313-20. · 3.56 Impact Factor
  • N Takahashi, A Iwahori, K Kawai, T Fukui
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    ABSTRACT: Falconensones A and B are new type of yellow pigment isolated from the mycelial extract of ascomycetous fungi, Emericella falconensis or Emericella fruticulosa, whose structures are similar to retinoic acid (RA). To date, biological activities of falconensones have not been reported. Herein, we reported that falconensone A inhibited growth of HL60 human leukemia cells, when used either singly or in combination with RA. Falconensone A alone did not induce differentiation of HL60 cells. However, falconesone A enhanced the differentiation of HL60 cells induced by 10 nM RA, and its effect was synergistic. On the other hand, falconensone B, the 4'-nor-methyl derivative of falconensone A, showed much lower activity than falconensone A on the inhibition of cell growth. In addition, synthetic derivatives of falconensone A, falconensone A p-bromophenylhydrazone and falconensone A dioxime, were more potent on the inhibition of cell growth and the induction of differentiation than natural falconensones A and B. These compounds induced differentiation of HL60 cells into monocyte/macrophage-like cells, different from granulocyte-like cells induced by RA. These results suggest that falconensone A may be a new type of antiproliferative agent, and that the methyl residue at the 4' position of the cyclopentenone ring of falconensone A may be necessary for biological activity. In addition, falconensone A enhanced RA-induced differentiation of HL60 cells, while its derivatives alone showed growth inhibition and induction of differentiation of HL60 cells. Based on these results, falconensone A and its derivatives may have clinical utility in the treatment of leukemia.
    Archives of Biochemistry and Biophysics 01/1999; 360(1):113-20. · 3.37 Impact Factor
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    ABSTRACT: All-trans-Retinoic acid (RA) induces differentiation and inhibits growth of many tumor types. Whereas the RA nuclear receptors mediate genomic effects of RA, there also are many nongenomic effects that do not have defined mechanisms. Some nongenomic effects of RA may involve retinoylation (RA acylation), a posttranslational modification of proteins occurring in many eukaryotic cell lines including the human breast cancer cell line MCF-7. To gain further knowledge of the role(s) of retinoylation, we studied the effects of tunicamycin (TM), an inhibitor of both protein N-glycosylation and palmitoylation, on growth and retinoylation in MCF-7 cells. We found that RA or TM alone inhibited growth of MCF-7 cells. Combinations of RA and TM inhibited growth synergistically. TM increased retinoylation and decreased palmitoylation. These results suggest that increased retinoylation and decreased glycosylation and palmitoylation may play a role in the synergistic inhibition of cell growth by combinations of TM and RA in MCF-7 cells. Furthermore, our results suggest that combinations of TM and RA may have clinical utility.
    Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 01/1997; 9(10):527-33. · 1.63 Impact Factor