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Studies on the regulation of cell cycle by allyl sulfides and their anticancer properties.

Research Project

Project/Area Number 15380097
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Food science
Research InstitutionNihon University

Principal Investigator

ARIGA Toyohiko  Nihon university, College of Bioresource Sciences, Professor, 生物資源科学部, 教授 (50096757)

Co-Investigator(Kenkyū-buntansha) SEKI Taiichiro  Nihon university, College of Bioresource Sciences, Associate Professor, 生物資源科学部, 助教授 (20187834)
KUMAGAI Hitomi  Nihon university, College of Bioresource Sciences, Associate Professor, 生物資源科学部, 助教授 (20225220)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2005: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥5,100,000 (Direct Cost: ¥5,100,000)
Keywordsdiallyl trisulfide / colon cancer / apoptosis / tubulin / cell cycle / garlic / allyl sulfide / LC-MS / MS / cancer / cancer cell / histone deacetylase
Research Abstract

Allyl sulfides are characteristic flavor components obtained from garlic. These sulfides are thought to be responsible for their epidemiologically proven anticancer effect on garlic eaters. This study was aimed at clarifying the molecular basis of this anticancer effect of garlic by using human colon cancer cell lines HCT-15 and DLD-1. The growth of the cells was significantly suppressed by diallyl trisulfide (DATS, HCT-15 IC_<50>=11.5 μM, DLD-1 IC_<50>=13.3 μM) ; however, neither diallyl monosulfide (DAS) nor diallyl disulfide (DADS) showed such effect. The proportion of HCT-15 and that of DLD-1 cells residing at G1 and S phases were decreased by DATS, and their population at the G2/M phase was markedly increased for up to 12h. The cells with a sub-G1 DNA content were increased thereafter. Caspase-3 activity was also dramatically increased by DATS. FACS analysis performed on the cells arrested at the G1/S boundary revealed cell cycle-dependent induction of apoptosis through the transition of G2/M to G1 phase by DATS. DATS inhibited tubulin polymerization in an in vitro cell-free system. DATS disrupted microtubule network formation of the cells and microtubule fragments could be seen at the interphase. Peptide mass mapping by LC-MS/MS analysis for DATS-treated tubulin demonstrated that there was a specific oxidative modification of cysteine residues Cys12β and Cys354β to form S-allylmercaptocysteine with a peptide mass increase of 72.1 Da. The potent antitumor activity of DATS was also demonstrated in the nude mice bearing HCT-15 xenografts. This is a first paper describing about intracellular target molecules directly modified by garlic components.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (21 results)

All 2006 2005 2004 2003 2002 Other

All Journal Article (16 results) Book (2 results) Patent(Industrial Property Rights) (1 results) Publications (2 results)

  • [Journal Article] Aantithrombotic and Anticancer Effects of Garlic-derived Sulfur Compounds - A review2006

    • Author(s)
      T.Ariga, T.Seki
    • Journal Title

      BioFactors (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ガーリックの抗ガン作用-香気成分によるチューブリンの修飾とアポトーシスの誘導2006

    • Author(s)
      関泰一郎, 有賀豊彦他
    • Journal Title

      科学と生物(日本農芸化学会誌) 44(5)

      Pages: 287-289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Aantithrombotic and Anticancer Effects of Garlic-derived Sulfur Compounds-Areview2006

    • Author(s)
      T.Ariga, T.Seki
    • Journal Title

      BioFactors (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anti-cancer effect of Garlic (in Japanese).2006

    • Author(s)
      T.Seki, T.Hosono, T.Fukao, T.Ariga
    • Journal Title

      KASEAA (Kagaku TO Seibutsu) 44(5)

      Pages: 287-289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Diallyl trisulfide suppresses the proliferation and induces apoptosis of human colon cancer cells through oxidative modification of β-tubulin.2005

    • Author(s)
      T.Hosono, T Ariga et al.
    • Journal Title

      J. Biol. Chem. 280・50

      Pages: 41487-41493

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Diallyl trisulfide suppresses the proliferation and induces apoptosis of human colon cancer cells through oxidative modification of beta-tubulin.2005

    • Author(s)
      T.Hosono, T.Fukao, J.Ogihara, Y.Ito, H.Shiba, T.Seki, T.Ariga
    • Journal Title

      J.Biol.Chem. 280(50)

      Pages: 41487-41493

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Diallyl trisulfide suppresses the proliferation and induces apoptosis of human colon cancer cells through oxidative modification of β-tubulin.2005

    • Author(s)
      T.Hosono
    • Journal Title

      J. Biol. Chem. 280・50

      Pages: 41487-41493

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Chemoprotective effect of diallyl trisulfide from garlic against carbon tetrachloride-induced acute liver injury of rats.2004

    • Author(s)
      T.Fukao, T.Ariga et al.
    • Journal Title

      Biofactors 21(1-4)

      Pages: 171-174

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Structure-function relation ship of allyl sulfide in the induction of phase II detoxification enzyme and liver injury induced by carbon tetrachloride.2004

    • Author(s)
      T.Fukao, T.Ariga et al.
    • Journal Title

      Food and Chemical Toxicology 42(5)

      Pages: 743-749

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Chemoprotective effect of diallyl trisulfide from garlic against carbon tetrachloride-induced acute liver injury of rats.2004

    • Author(s)
      T.Fukao, T.Hosono, S.Misawa, T.Seki, T.Ariga
    • Journal Title

      Biofactors 21(1-4)

      Pages: 171-174

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Structure-function relation ship of allyl sulfide in the induction of phase II detoxification enzyme and liver injury induced by carbon tetrachloride.2004

    • Author(s)
      T.Fukao, T.Hosono, S.Misawa, T.Seki, T.Ariga
    • Journal Title

      Food and Chemical Toxicology 42(5)

      Pages: 743-749

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Chemoprotective effect of diallyl trisulfide from garlic against carbon tetrachloride-induced acute liver injury of rats.2004

    • Author(s)
      Fukao, T.et al.
    • Journal Title

      Biofactors 21・1-4

      Pages: 171-174

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachloride2004

    • Author(s)
      Fukao, T.et al.
    • Journal Title

      Food and Chemical Toxicology 42・5

      Pages: 743-749

    • Related Report
      2004 Annual Research Report
  • [Journal Article] がんの予防を目指した「食」と「栄養」のバイオサイエンス : 食用植物由来含硫化合物の抗がん作用メカニズムとがんの予防2003

    • Author(s)
      関 泰一郎, 有賀豊彦 他
    • Journal Title

      日本農芸化学会誌 77(11)

      Pages: 1113-1115

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anti-cancer effect of sulfur-containing compound derived from edible plant and cancer prevention (in Japanese).2003

    • Author(s)
      T.Seki, T.HOsono, T.Fukao, T.Masaki, K.Hara, T.Ariga
    • Journal Title

      KASEAA (Kagaku TO Seibutsu) 77(11)

      Pages: 1113-1115

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Aantithrombotic and Anticancer Effects of Garlic-derived Sulfur Compounds-Areview

    • Author(s)
      T.Ariga
    • Journal Title

      BioFactors (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Book] Asian Functional Foods (Editors, John Shi, Chi-Tang Ho, Fereidoon Shahidi),2005

    • Author(s)
      T.Ariga, T.Seki
    • Total Pages
      647
    • Publisher
      CRC Press,New York, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Asian Functional Foods(Editors, John Shi, Chi-Tang Ho, Fereidoon Shahidi),2005

    • Author(s)
      T.Ariga
    • Total Pages
      647
    • Publisher
      CRC Press, New York, USA
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] がん細胞増殖抑制剤2002

    • Inventor(s)
      有賀 豊彦, 関 泰一郎, 細野 崇
    • Industrial Property Rights Holder
      日本大学
    • Industrial Property Number
      2002-159194
    • Filing Date
      2002-05-31
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Fukao, T., et al.: "the effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachloride"Food and Chemical Toxicology. 42・5. 743-749 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 関 泰一郎 他: "食用植物由来含硫化合物の抗がん作用メカニズムとがんの予防"日本農芸化学会誌. 77・11. 1113-1115 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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