| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
This study was examined the isolation of antitumor substances from natural medicinal drugs as the targets with the inhibition of tumor-induced neovascularization and the stimulation of immune function. The summary of the research results were described as follows ;
1.Isolation of anti-angiogenic substance from Agaricus blazein Murill : Its antitumor and antimetastatic actions
Two anti-angiogenic substances (A-1 and A-2) were isolated from A.blazei using as assay system of angiogenesis induced by Matrigel supplemented with vascular endothelial growth factor (VEGF). A-1 was identified as sodium pyroglutamate. A-1 inhibited tumor growth and metastasis to the lung in Lewis lung carcinoma (LLC)-bearing mice. Futhermore, the reduction of the numbers of splenic lymphocytes, CD4+ and CD8+ T cells in LLC-bearing mice was inhibited by the oral administration of A-1. Furthermore, A-1 increased the numbers of CD8+ T and natural killer cells invading the tumors. These results suggest that the antitum
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or and antimetastatic actions of A-1 (sodium pyroglutamate) may be associated with inhibition of the reduction of immune response caused by the tumor growth and tumor-induced neovascularization.
2.Isolation of antitumor substance, 4-hydroxyderricin from Angelica keiskei roots
In the preset study, two yellow substances (I and II) were isolated from Anglica keiskei roots as antitumor substances, and then I and II were identified as xantoangelol and 4-hydroxyderricin. We recently reported that xanthoangelol inhibited tumor growth and metastasis to the lung through the inhibition of tumor-induced angiogenesis. And then, the antitumor and antimetastic actions of 4-hydroxyderricin were examined using LLC-bearing mice. 4-Hydroxyderricin inhibited the tumor growth in subcutaneous LLC-implanted mice and inhibited the lung metastasis and prolonged the survival time in mice after the removal of subcutaneous tumors by surgical operation. In addition, 4-hydroxyderricin inhibited the reduction of numbers of lymphocytes, CD4^+T, CD8^+T and natural killer (NK) cells in the spleen of tumor-removed mice. These results suggest that the antitumor and antimetastatic activities of 4-hydroxyderricin may be modulated by the immune system.
3.Isolation and structural determination of novel eicosapentaenoic acid (EPA) derivatives and its antitumor and antimetastatic actions
EPA derivatives formed during accelerated stability testing of EPA, inhibited the tumor growth and metastasis to the lung in LLC-bearing mice through the anti-angiogenesis and the stimulation immune function. EPA derivatives are composed of a mixture of a newly identified EPA ethylester dimer and EPA hydroxyethylester, and known EPA and EPA ethylesters. EPA ethylester dimer and EPA hydroxyethylester increased the O2- production by LLC cells, and the effects of EPA ethylester dimer was stringer than that of EPA ethylester. Therefore, these findings suggest that EPA ethylester dimer and EPA hydroxyethylester formed EPA ethylester may be a candidate compound for antitumor agents as well as the antitumor action of EPA ethylester. Less
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