Lavandulylflavonoids: a new class of in vitro apoptogenic agents from Sophora flavescens.

The root of Sophora flavescens has been reported to possess antitumor activity in Sarcoma 180, lymphoid leukemia 1210 and melanotic melanoma. We have isolated four cytotoxic flavonoids with a lavandulyl side-chain at C8 and tested for their effects on human myeloid leukemia HL-60 cells and human hepatocarcinoma HepG2 cells, in terms of inhibition of proliferation and induction of apoptosis. They showed potent antiproliferative effects with IC(50) values from 11.3 microM to 18.5 microM in HL60 cells and from 13.3 microM to 36. 2 microM in HepG2 cells. Treatment of HL-60 cells with the lavandulylflavonoids induced apoptosis in a dose-dependent manner. Apoptosis was judged by the detection of DNA fragmentation by agarose gel electrophoresis and the degree of apoptosis was quantified by a sandwich enzyme immunoassay. The hydration of C4"'C5"' double bond with or without C3 hydroxylation caused a complete loss of cytotoxicity. These results suggest that the lavandulyl side-chain is essential for the activity of the flavonoids isolated from S. flavescens which may be used as cancer chemotherapeutic and chemopreventive agents.