| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Research Abstract |
In the present study, we investigated the active constituents with anti-invasive, matrix metalloproteases (MMPs) production inhibitory, differentiation-inducing activities from medicinal plants that have been used for anti-cancer and longevity.
1.The MeOH extract and EtOAc-soluble fraction traditional Thai medicine, the stems of Erycibe expansa (Convolvulaceae) were found to inhibit invasion of HT1080 cells through Matrigel-coated filters in vitro and proliferation of human fibroblast (HT1080) and human leukemia cell (U937) cells. Through bioassay-guided separation, four principal rotenoids [deguelin (1), tephrosin (2), rotenone (3), 12a-hydroxyrotenone (4)] together with various isoflavones and pterocarpanes were isolated from the EtOAc fraction. Among them, 1-4 inhibited the invasion of HT1080 cells at 3-30 μM after 24 h incubation, and they also inhibited proliferation of HT1080 and human leukemia U937 cells after 48 h incubation. With regard to their action mechanism, 1-4 (1-10 μM)
… More
inhibited release of proMMP-9 in the medium using a gelatin zymography. Furthermore, compounds 1 and 2 (10 μM) induced the differentiation of HL-60 cells using NBT reduction test.
2.The methanolic extract and its alkaloid fraction from the rhizomes of Nuphar pumilum were found show cytotoxic effects on U937, mouse melanoma cell (B16F10), and HT1080 in the experiments of their anti-invasion. Dimeric sesquiterpene thioalkaloids with the 6-hydroxyl group (6-hydroxythiobinupharidine, 6,6'-dihydroxythiobinupharidine, 6-hydroxythionuphlutine B) showed substantial cytotoxic activity at a concentration of 10 μM, and several structural requiremwnts for the activity were clarified. Apoptosis of U937 was immediately observed within 1 h after treatment of 6-hydroxythiobinupharidine and pathway via caspase-8 was found to be involved.
3.Furthermore, new diterpene alkaloids, nigellamines were isolated from the seeds of Nigella sativa that have been used for cancer treatment and their chemical structures were determined. 1'S-1'-Acetoxychavicol acetate and various related compounds were found to inhibit activation of NF-κB, suggesting antitumor activity. Less
|
