Antitumor agents XLI: Effects of eupaformosanin on nucleic acid, protein, and anaerobic and aerobic glycolytic metabolism of Ehrlich ascites cells.
The major effect of eupaformosanin as an antineoplastic agent on Ehrlich ascites cell metabolism was to inhibit deoxyribonucleic acid synthesis, specifically at deoxyribonucleic acid polymerase and thymidylate synthetase enzymatic sites. Both pyrimidine and purine systems of Ehrlich ascites were marginally inhibited. Ribonucleic acid synthesis and messenger and ribosomal polymerase activities also were suppressed. Cyclic adenosine monophosphate levels were increased significantly, which correlated with the drastic reduction of histone phosphorylation. Eupaformosanin also suppressed a number of glycolytic and Krebs cycle enzymes as well as oxidative phosphorylation in vitro. All of the inhibited enzymes are known thiol-bearing enzymes that can undergo a Michael-type addition with the alpha-methylene-gamma-lactone moiety of eupaformosanin, as shown with other sesquiterpene lactones.
D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009363:Neoplasm Proteins / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D013729:Terpenes; C025216:eupaformosanin