| Kinase Assay: |
| Mol Cancer Ther. 2006 Nov;5(11):2666-75. | | Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expression.[Pubmed: 17121913] | Matrix metalloproteinase (MMP)-9 plays a key role in tumor invasion. Inhibitors of MMP-9 were screened from Metasequoia glyptostroboides (Dawn redwood) and one potent inhibitor, Isoginkgetin, a biflavonoid, was identified.
METHODS AND RESULTS:
Noncytotoxic levels of Isoginkgetin decreased MMP-9 production profoundly, but up-regulated the level of tissue inhibitor of metalloproteinase (TIMP)-1, an inhibitor of MMP-9, in HT1080 human fibrosarcoma cells. Further studies showed that Isoginkgetin regulated MMP-9 production via PI3K/Akt/NF-kappaB pathway, as evidenced by the findings that Isoginkgetin inhibited activities of both Akt and NF-kappaB. PI3K/Akt is a well-known key pathway for cell invasion, and Isoginkgetin inhibited HT1080 tumor cell invasion substantially. Isoginkgetin was also quite effective in inhibiting the activities of Akt and MMP-9 in MDA-MB-231 breast carcinomas and B16F10 melanoma. Moreover, Isoginkgetin treatment resulted in marked decrease in invasion of these cells.
CONCLUSIONS:
In summary, PI3K/Akt is a major pathway for MMP-9 expression and Isoginkgetin markedly decreased MMP-9 expression and invasion through inhibition of this pathway.
This suggests that Isoginkgetin could be a potential candidate as a therapeutic agent against tumor invasion. | | J Endocrinol. 2007 Sep;194(3):569-78. | | Isoginkgetin enhances adiponectin secretion from differentiated adiposarcoma cells via a novel pathway involving AMP-activated protein kinase.[Pubmed: 17761896] |
METHODS AND RESULTS:
We identified Isoginkgetin, a compound derived from the leaves of Ginkgo biloba, to up-regulate adiponectin secretion with potency comparable to that of rosiglitazone, a known modulator of adiponectin production. However, unlike rosiglitazone, peroxisome proliferators-activated receptor gamma activity seems not required for the action of Isoginkgetin, and Isoginkgetin has only a slight effect on adipogenesis, which makes it an attractive candidate for anti-diabetic treatment. Further investigation revealed that both Isoginkgetin and rosiglitazone activate AMP-activated protein kinase (AMPK) in adipocytes.
CONCLUSIONS:
Our findings suggest a novel mechanism for the elevation of adiponectin by Isoginkgetin, which is different from that of rosiglitazone. Furthermore, this novel mechanism for adiponectin regulation involving AMPK can potentially facilitate new understanding of metabolic diseases and identification of new targets, as well as agents that increase plasma adiponectin levels. |
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