A biflavonoid inhibitor of pre-mRNA splicing
Isoginkgetin is a biflavonoid that has been found in G. biloba and is an inhibitor of pre-mRNA splicing.1 Isoginkgetin (33 μM) reduces the activity of an mRNA-dependent luciferase reporter by 5-fold, shifts the composition of total RNA extract from predominantly mRNA to pre-mRNA, and arrests cell growth in HEK293 cells. Isoginkgetin (10 μM) suppresses mouse lymphocyte proliferation induced by concanavalin A and LPS by approximately 87 and 90%, respectively.2 It also suppresses arachidonic acid release induced by phorbol 12-myristate 13-acetate and the calcium ionophore A23187 by 32.5 and 48.4%, respectively, in rat peritoneal macrophages when used at a concentration of 10 μM.3 Isoginkgetin (5-20 μM) reduces matrix metalloproteinase-9 (MMP-9) activity, expression, and mRNA levels in and decreases cell invasion by HT1080 fibrosarcoma cells in a concentration-dependent manner.4
1.O'Brien, K., Matlin, A.J., Lowell, A.M., et al.The biflavonoid isoginkgetin is a general inhibitor of pre-mRNA splicingJ. Biol. Chem.283(48)33147-33154(2008) 2.Lee, S.J., Choi, J.H., Son, K.H., et al.Suppression of mouse lymphocyte proliferation in vitro by naturally-occurring biflavonoidsLife Sci.57(6)551-558(1995) 3.Lee, S.J., Son, K.H., Chang, H.W., et al.Inhibition of arachidonate release from rat peritoneal macrophage by biflavonoidsArch. Pharm. Res.20(6)533-538(1997) 4.Yoon, S.-O., Shin, S.S., Lee, H.-J., et al.Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expressionMol. Cancer Ther.5(11)2666-2675(2006)
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