Project/Area Number |
13556016
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Bioproduction chemistry/Bioorganic chemistry
|
Research Institution | Tohoku University |
Principal Investigator |
MIYAZAWA Teruo Tohoku Universty, Graduate School of Life Science and Agriculture, Professor, 大学院・農学研究科, 教授 (20157639)
|
Co-Investigator(Kenkyū-buntansha) |
HADA Takahiko Bizen Chemical Co.LTD Acting head of a section, 開発研究部, 課長代理
INOUE Yoshinori Bizen Chemical Co.LTD Manager, 開発研究部, 部長
TSUDA Hroyuki National cancer center, Experimental Pathology and Chemotherapy Division, Chief, 化学療法部, 部長
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2002: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2001: ¥4,400,000 (Direct Cost: ¥4,400,000)
|
Keywords | Conjugated fatty acid / Conjugated triene / Colon cancer / Apoptosis / Lipid peroxidation / Anticarcinogenesis / Lipid metabolism / ヌードマウス / 酸化ストレス / 大量調製法 |
Research Abstract |
We found out that conjugated eicosapentaenoic acid (CEPA) and conjugated docosahexaenoic acid (CDHA) with conjugated trienoic structure, have the strongest cytotoxic effect selectively on human tumor cell lines. The incorporation of these conjugated fatty acids is sufficient to increase the sensitivity to oxidative damage that is indicative for apoptotic cell death. The CEPA with triene structure, prepared by aikaline treatment, showed intensive toxicity with DLD-1 cell (colorectal adenocarcinoma) -transplanted tumor in male athymic nude mice. The anticarcinogenic activity involved membrane phospholipid peroxidation. CEPA induced DNA fragmentation in DLD-1 cell-transplanted tumor in nude mice, indicating the involvement of apoptosis in the anticarcinogenic mechanism. The occurrence of a significant amount of 9, 11-conjugated linoleic acid (CLA, 9, 11-18:2) was confirmed in the liver and plasma lipids of rats fed a 1% (w/w % of diet) eleostearic acid (ESA, 9, 11, 13-18:3) diet. The chemical structure of 9, 11-CLA was identified by gas chromatography-electron impact mass spectrometry after its conversion to a 4, 4-dimethyloxazoline derivative. The concentration of CLA in the total fatty acids of the liver and plasma lipids reached to 1% for each in the CLA-supplemented rats, while reaching 3.2% and 2.5%, respectively, in the ESA-supplemented rats. The α-ESA was shown to be metabolized partially to CLA via a delta 13-saturation reaction in the rat. Some biological activities observed in α-ESA-fed animals may be ascribed also to CLA that is formed from ESA in the body.
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