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Role of polyamines on cell proliferation and differentiation

Research Project

Project/Area Number 06044034
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionChiba University

Principal Investigator

IGARASHI Kazuei  Chiba University, Pharmacecutical Sciences, professor, 薬学部, 教授 (60089597)

Co-Investigator(Kenkyū-buntansha) KASHIWAGI Keiko  Chiba University, 薬学部, 助手 (80169424)
STEFANIA Biondi  University of Bologna, 理学部, 助教授
NELLO Bagni  University of Bologna, 理学部, 教授
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1995: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1994: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsPolyamine / Spermidine / Spermine / Protein synthesis / Transport / Cell proliferation / Cell differentiation
Research Abstract

1. Physiological functions of spermidine acetyltransferase in Escherichia coli have been studied using the spermidine acetyltransferase (speG) gene-deficient mutant CAG2242 and the cloned speG gene. The growth of E.coli CAG2242 was normal in the presence and absence of 0.5 mM spermidine. However, cell viability of E.coli CAG2242 at 48 h after the onset of growth decreased greatly by the addition of 0.5 mM spermidine. The amount of spermidine accumulated in the cells was approximately 3-fold that in the cells grown in the absence of spermidine. Transformation of the cloned speG gene to E.coli CAG2242 recovered the cell viability. The accumulation of spermidine caused a decrease in protein synthesis but not in DNA and RNA synthesis at 28 h after the onset of growth. The synthesis of several kinds of proteins was particularly inhibited. They included ribosome mudulation factor and OmpC protein. Since the ribosome modulation factor is essential for cell viability at the stationary phase of … More growth, the decrease in the protein was thought to be one of the reasons for the decrease in cell viability. The decrease in the ribosome modulation factor mainly occured at the translational level.
2. Effects of 1,15-bis (ethylamino) -4,8,12-triazapentadecane (BE3333) on the growth of tumor cells were studied in in vitro systems and with tumor xenografts in mice. BE3333 suppressed ornithine decarboxylase and S-adenosylmethionine decarboxylase, induced spermidine/spermine N^1-acetyltransferase, and thus decreased the amount of polyamines. BE3333 accumulated in cells at a concentration 3-5-fold that of spermine in control cells. The accumulated BE3333 inhibited protein synthesis, especially mitochondrial protein synthesis, and decreased the amount of ATP.The inhibition of protein synthesis was correlated with the subsequent inhibition of cell growth. BE3333 showed inhibitory effects in in vitro systems against the growth of mouse FM3A mammary carcinoma cells, human SW480 and SW620 colon tumor cells, Lu-65A and A549 lung tumor cells, MCF-7 breast tumor cells, and MALME-3M and A375 melanoma cells at a range of 0.5-10 muM.Intravenous (30 mg/kg) or i. p. (50 mg/kg) daily injections of BE3333 for 5 days greatly suppressed the growth of human tumor SW620 xenotrasplanted into nude mice. BE3333 also showed inhibitory effects against the growth of lung tumors (Lu-65, Lx-1, Lc-1, and Lu-61), stomach tumors (Sc-6 and St-15), and melanoma (SEKI) xenotransplanted into nude mice. The results indicate that BE3333 is effective against both rapid-and slow-growting tumors, with reasonable short-term host toxicity. Less

Report

(2 results)
  • 1995 Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] J.Fukuchi et al.: "Decrease in cell viability due to the accumulation of srermidine in spermidine acetyltransferase-deficient mutant of Escherichia coli." J.Biol.Chem.270. 18831-18835 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Wada et al.: "Ribosome modulation factor : Stationary growth phase-specific inhibitor of ribosome functions from Escherichia coli." Biochem.Biophys.Res.Commun.214. 410-417 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Igarashi et al.: "Inhibition of the growth of various human and mouse tumor cells by 1,15-bis (ethylamino) -4,8,12-triazapentadecane." Cancer Res.55. 2615-2619 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.He et al.: "Inhibition of cell growth by combination of α-difluoromethylorniithine and an inhibitor of spermine synthase." J.Biochem.117. 824-829 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Igarashi et al.: "Antagonist properties of polyamines and bis (ethyl) polyamines at N-methyl-D-aspartate receptors." J.Pharmacol.Exp.Ther.272. 1101-1109 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Kakinuma et al.: "Cloning of the gene encoding a putative serine/threonine protein kinase which enhances spermine uptake in Saccharomyces cerevisiae." Biochem.Biophys.Res.Commun.216. 985-992 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] J.Fukuchi et al.: "Decrease in cell viability due to the accumulation of spermidine in spermidine acetyltransferase-deficient mutant of Escherichia coli." J.Biol. Chem.270. 18831-18835 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Wada et al.: "Ribosome modulation factor : Stationary growth phase-specific inhibitor of ribosome functions from Escherichia coli." Biochem. Biophys. Res. Commun.214. 410-417 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Igarashi et al.: "Inhibition of the growth of various human and mouse tumor cells by 1,15-bis (ethylamino) -4,8,12-triazapentadecane." Cancer Res.55. 2615-2619 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.He et al.: "Inhibition of cell growth by combination of alpha-difluoromethyl-ornithine and an inhibitor of spermine synthase." J.Biochem.117. 824-829 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Igarashi et al.: "Antagonist properties of polyamines and bis (ethyl) polyamines at N-methyl-D-aspartate receptors." J.Pharmacol. Exp. Ther.272. 1101-1109 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Kakinuma et al.: "Cloning of the gene encoding a putative serine/threonine protein kinase which enhances spermine uptake in Saccharomyces cerevisiae." Biochem. Biophys. Res. Commun.216. 985-992 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.He et al.: "Correlation between the inhibition of cell growth by bis(ethyl)polyamine analogues and the decerease in the function ofmitochondria." Eur.J.Biochem.221. 391-398 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Suzuki et al.: "Antizyme protects against abnormal accumulation and toxicity of polyamines in ormithine decarboxylase-overproducing cells." Proc.Natl.Acad.Sci.USA. 91. 8930-8934 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] J.Fukuchi et al.: "Properties and structure of spermidine acetyltransferase in Escherichia coli." J.Biol.Chem.269. 22581-22585 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] I.Ishii et al.: "Decrease in spermidine content during logarithmic phase of cell Growth delays spore formation of Bacillus subtilis." Cell.Mol.Biol.40. 925-931 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Maruyama et al.: "Polyamine-sensitive magnesium transport in Saccharomyces cerevisiae." Biochim.Biophys.Acta.1194. 289-295 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Kashiwagi et al.: "Involvement of ribonucrease III in the enhancement of expression of the speF-potE operon encoding inducible ornithine decarboxylase and polyaminetransport protein." Biochem.Biophys.Res.Commun.200. 591-597 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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