[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 0.35 mumol/L respectively. RAN inhibited the incorporation of 3H-labeled precursors into DNA and RNA of L1210 cells. RAN (15 mumol/L) markedly decreased DNA synthesis catalyzed by DNA polymerase 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.
Li
R Z
RZ
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing.
Ji
X J
XJ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D005609:Free Radicals; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D007939:Leukemia L1210 / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology; D008759:Methylglycosides / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D004365:Drugs, Chinese Herbal; D005609:Free Radicals; D005663:Furans; D008759:Methylglycosides; D004247:DNA; C039859:ranunculin; D010100:Oxygen