Effects of Hibarimicins and Hibarimicin-Related Compounds Produced by Microbispora on v-Src Kinase Activity and Growth and Differentiation of Human Myeloid Leukemia HL-60 Cells.

• CHO SUNG IG

  Department of Bioactive Molecules, National Institute of Infectious Diseases

• FUKAZAWA HIDESUKE

  Department of Bioactive Molecules, National Institute of Infectious Diseases

• HONMA YOSHIO

  Department of Chemotherapy, Saitama Cancer Center Research Institute

• KAJIURA TAKAYUKI

  Biotechnology Research Center, Toyama Prefectural University

• HORI HIROSHI

  Department of Applied Biological Chemistry, Tamagawa University

• IGARASHI YASUHIRO

  Biotechnology Research Center, Toyama Prefectural University

• FURUMAI TAMOTSU

  Biotechnology Research Center, Toyama Prefectural University

• OKI TOSHIKAZU

  Biotechnology Research Center, Toyama Prefectural University

• UEHARA YOSHIMASA

  Department of Bioactive Molecules, National Institute of Infectious Diseases

抄録

We studied the effects of hibarimicins and hibarimicin-related compounds produced by Microbispora rosea subsp. hibaria [glycosides (hibarimicins A, B, C, D, E, G, H and I) and aglycon (hibarimicinone)] or compounds produced by its mutants [glycosides (HMP-P4 and -Y6), aglycons (HMP-P1 and -Y1) and shunt products (HMP-M1, M2, M3 and -M4)] on v-Src tyrosine kinase and growth and differentiation of human myeloid leukemia HL-60 cells. Among them, hibarimicin B was a strong and the most selective v-Src kinase inhibitor with differentiation inducing activity of HL-60 cells. Hibarimicin E similarly induced HL-60 cell differentiation but had no v-Src kinase inhibitory activity. Hibarimicinone was the most potent v-Src kinase inhibitor, although less selective, and did not induce differentiation of HL-60 cells. Hibarimicin B competitively inhibited ATP binding to the v-Src kinase, but hibarimicinone showed noncompetitive inhibition. These two compounds, however, showed similar mixed types of inhibition against a Src substrate binding to the v-Src kinase. Altogether, these results suggest that signaling molecules other than Src might be more important in the differentiation induction of HL-60 cells.

収録刊行物

• The Journal of Antibiotics

  The Journal of Antibiotics 55 (3), 270-278, 2002

  公益財団法人 日本感染症医薬品協会

キーワード

• Drug Discovery
• Pharmacology

詳細情報

• CRID: 1390282679127774080
• NII論文ID: 130003503960
• NII論文ID: 10008472256
• NII書誌ID: AA0069330X
• DOI: 10.7164/antibiotics.55.270
• COI: 1:CAS:528:DC%2BD38Xis1aisb0%3D
• ISSN: 18811469
• ISSN: 00218820
• ISSN: http://id.crossref.org/issn/00218820
• PubMed: 12014442
• Web Site: https://search.jamas.or.jp/link/ui/2002189756
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可