In vitro cytotoxic activity of 1-decarboxy-3-oxo-ceanothic acid in a human ovarian adenocarcinoma cell line.
The effect of a novel pentacyclic triterpene, 1-decarboxy-3-oxo-ceanothic acid (DOCA) on DNA synthesis, DNA degradation and programmed cell death was examined in human ovarian adenocarcinoma (OVCAR-3) cells. OVCAR-3 cells exposed to various concentrations of DOCA for 30 h displayed a dose-dependent inhibition of DNA synthesis. Morphologically, treatment with 10 microg/ml of DOCA for 24 h and 72 h resulted respectively in reduction in cell volume and condensation of nuclear structures. By agarose gel analysis, DNA fragmentation with the characteristic pattern of inter-nucleosomal ladder was observed after cells were treated with 2.5 microg/ml of DOCA for 24 h. Both cell death and DNA fragmentation caused by this compound were partially inhibited by the protein synthesis inhibitor cycloheximide, suggesting that the apoptotic process caused by DOCA requires synthesis of new proteins. On the other hand, no apparent double-stranded DNA breaks were detected after cells were incubated with 2.5 microg/ml of DOCA for 24 h, indicating that DNA damage was not a preceding event for apoptosis induced by this compound. Taken together, our results demonstrate that the cytotoxic effect of DOCA is mediated, at least in part, by the induction of apoptosis.
Su
Y
Y
Institute of Pharmacology, College of Life Science, National Yang-Ming University, Shi-Pai, Taipei, Taiwan, ROC.
Chang
C L
CL
Lee
S S
SS
Chen
W C
WC
Huang
C F
CF
D000230:Adenocarcinoma / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D009707:Nucleosomes / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000473:pathology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C115059:1-decarboxy-3-oxoceanothic acid; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009707:Nucleosomes; D011500:Protein Synthesis Inhibitors; D014315:Triterpenes; D003513:Cycloheximide