Induction of DNA damage in Ehrlich ascites tumour cells by exposure to eupatoriopicrin.
The sesquiterpene lactone eupatoriopicrin (EUP) from Eupatorium cannabinum L. has been shown to be cytotoxic in a glutathione (GSH)-dependent way. In order to assess possible DNA damage as a cause for cell death, the study reported was initiated. After 2 hr incubation of Ehrlich ascites tumour cells with EUP, the DNA damage, determined by the use of an alkaline DNA unwinding method, followed by hydroxylapatite column chromatography of degraded DNA, was observed at concentrations only slightly higher than those causing cell death in a clonogenic assay. The amount of EUP, requested to demonstrate DNA damage after a 24-hr post-incubation period lay within the concentration range that was effective in the clonogenic assay (1-10 micrograms/ml). Glutathione (GSH) depletion of the cells to about 99%, by use of buthionine sulphoximine (BSO), enhanced the extent of DNA damage. It is concluded that EUP-induced DNA damage may play a role in the observed cytotoxicity.
Woerdenbag
H J
HJ
Department of Pharmacognosy, University Centre for Pharmacy, University of Groningen, The Netherlands.
van der Linde
J C
JC
Kampinga
H H
HH
Malingré
T M
TM
Konings
A W
AW
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D012717:Sesquiterpenes; C032660:eupatoriopicrine