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

The root of Sophora flavescens has been reported to possess antitumor activ ity in Sarcoma 180, lymphoid leukemia 1210 and melanotic melanoma, We have isolated four cytotoxic flavonoids with a lavan-dulyl side-chain at C8 and tested for their effects on human myeloid leukemia HL-60 cells and human he patocarcinoma HepG2 cells, in terms of inhibition of proliferation and indu ction of apoptosis, They showed potent antiproliferative effects with IC50 values from 11.3 mu M to 18.5 mu M in HL60 cells and from 13.3 mu M to 36.2 mu M in HepG2 cells, Treatment of HL-60 cells with the lavandulyflavonoids induced apoptosis in a dose-dependent manner, Apoptosis was judged by the detection of DNA fragmentation by agarose gel electrophoresis and the degre e of apoptosis was quantified by a sandwich enzyme immunoassay. The hydrati on of C4 "'C5 "' double bond with or without C3 hydroxylation caused a comp lete loss of cytotoxicity. These results suggest that the lavanduyl side-ch ain is essential for the activity of the flavonoids isolated from S. flaves cens which may be used as cancer chemotherapeutic and chemopreventive agent s. (C) 2000 Elsevier Science Ltd. All rights reserved.