| Project/Area Number |
15380097
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Food science
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| Research Institution | Nihon University |
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Principal Investigator |
ARIGA Toyohiko Nihon university, College of Bioresource Sciences, Professor, 生物資源科学部, 教授 (50096757)
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| 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)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| 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)
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| Keywords | diallyl trisulfide / colon cancer / apoptosis / tubulin / cell cycle / garlic / allyl sulfide / LC-MS / MS / cancer / cancer cell / histone deacetylase |
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| 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.
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