THE CYTOTOXICITY AND ACTION MECHANISM OF RANUNCULIN IN VITRO

This paper describes the cytotoxicity of ranunculin(RAN) and its mechanism of action. The IC₅₀ of RAN against the KB and Bel₇₄₀₂ cells in colony test were found to be 0. 21 and 0. 35μmol/L respectively. RAN inhibited the incorporation of ³H-labeled precursors into DNA and RNA of L₁₂₁₀ cells. RAN (15 μmol/L) markedly decreased DNA synthesis catalyzed by DNA ploymerase Ⅰ and promoted the generation of superoxide anions in DMSO/KO₂ system. In the meantime, SOD and CAT were shown to partly revoke the inhibitory effects of RAN upon the incorporation of ³H-TdR into DNA. No direct reaction between RAN and DNA template was observed and no effect of RAN on DNA TOPO Ⅱ or RNA polymerase Was found. Our results suggest that the cytotoxicity of RAN in vitro may be due to inhibition of DNA polymerase and increase of oxygen free radicals.