| Project/Area Number |
13660114
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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 |
食品科学・栄養科学
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| Research Institution | Hokkaido University |
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Principal Investigator |
SONOYAMA Kei Hokkaido Univ., Grad. School of Agr., Assist. Prof., 大学院・農学研究科, 助手 (90241364)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Keywords | Activin A / Butyrate / Colorectal cencer / HT-29 / Smad / IEC-6 / ビタミンD |
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| Research Abstract |
1. Colorectal tumor-suppressing effect of dietary fiber has been reportedly associated with its fermentation product butyrate. The present study investigated whether activin A mediates butyrate-induced growth arrest and apoptosis in colon cancer cells.
2. Butyrate induced G1 arrest and apoptosis in human colon cancer cell line HT-29. Butyrate also stimulated activin A gene in time-and dose-dependent manner. Because trichostain A also stimulated activin A gene, the effect of butyrate is possibly associated with the inhibition of histone acetylase. Stimulation of activin A gene by butyrate seems to be specific to cancer cells, as normal cell lines showed no response to butyrate.
3. Exogenous activin A did not aggect the growth of HT-29 cells. Immuneprecipitation coupled with Western blotting revealed that activin A induced phosphorylation of smad2 but not complex formation of smad2/3/4 in HT-29 cells. The cell line expressed neither smad4 mRNA nor protein. It is thus suggested that unresponsiveness to activin A in HT-29 cells is due to mutation of smad4.
4. Taken together, upregulated activin A by butyrate in colon cancer cells acts as paracrine factor rather than autocrine factor. Thus activin A does not mediate butyrate-induced growth arrest and apoptosis in colon cancer cells.
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