2005 Fiscal Year Final Research Report Summary
Study on the biotinidase competitive inhibition constant in liver cancer, and its control by a sugar chain
| Project/Area Number |
16590575
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Gunma University |
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Principal Investigator |
NAGAMINE Takeaki GUNMA UNIVERSITY, Faculty of Medicine, Professor, 医学部, 教授 (90180520)
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| Co-Investigator(Kenkyū-buntansha) |
HAYAKAWA Koh National Research Institute for Child Health and Development, Section Head, 小児代謝病態研究所, 室長(研究職) (80192277)
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| Project Period (FY) |
2004 – 2005
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| Keywords | fucoidan / cultured hepatoma cell line / biotinidase / α fetoprotein |
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| Research Abstract |
1. Anti-tumor effect of fucoidan on cultured hepatoma cell lines
According to the results of MTT assay, natural fucoidan showed an inhibitory effect in dose dependent manner on Hep G2 cells, Huh7 cells, and Chang cells (normal hepatocyte). The inhibitory effect of fucoidan on cell proliferation is similar among these three cell lines. Large molecular fucoidan exerted a stronger inhibitory effect on Chang cells and Huh7cells than in HepG2 cells. Judging from TUNEL stain using HepG2 cells and Chang cells, apoptosis induction by natural fucoidan was milder than that by nigero-oligosaccharide.
2. Effect of fucoidan on a fetoprotein production (a tumor marker for hepatocellular carcinoma)
HepG2cells and Huh7cells were treated with various concentrations of fucoidan (0%, 1%, 2%, 4%, 10%, 20%), and medium a fetoprotein levels were determined after 24 h after treatment. Consequently, fucoidan. reduced medium α fetoprotein levels of HepG2 cells in a dose dependent manner. Comparing to native and small molecular fucoidans, large molecular fucoidan reduced predominantly α fetoprotein levels. Medium α fetoprotein levels were decrease by natural, large molecular and small molecular fucoidans in dose dependent manner. The western blotting of α fetoprotein in Huh7 cells showed marked reduction of α fetoprotein by natural fucoidan, but not by nigero-oligosaccharide. On the other hand, nigero-oligosaccharide did not decrease α fetoprotein levels of Huh? cells and HepG2 cells.
3. Changes of biotinidase enzyme activity by fucoidan
Natural fucoidan markedly decreased biotinidase Ki of HepG2 cells and Huh7 cells.
These data suggested that fucoidan may demonstrate anti-tumor activity through modulating the enzyme kinetics of biotinidase.
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