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Role of membrane lipid composition in the cytotoxicity of the sesquiterpene lactone eupatoriopicrin
Author(s) -
Van Der Linde Joost C. C.,
Woerdenbag Herman J.,
Malingré Theo M.,
Kampinga Harm H.,
Konings Antonius W. T.
Publication year - 1993
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.2650070207
Subject(s) - trypan blue , arachidonic acid , lipid peroxidation , biochemistry , polyunsaturated fatty acid , cytotoxicity , sesquiterpene lactone , lysis , linoleic acid , biology , chemistry , microbiology and biotechnology , fatty acid , cell , antioxidant , in vitro , sesquiterpene , stereochemistry , enzyme
The aim of the present study was to investigate a possible role of lipid peroxidation in the cytotoxicity of eupatoriopicrin, the principal sesquiterpene lactone from Eupatorum cannabinum L. Incorporation of arachidonic acid acyl chains in the phospholipids of cellular membranes of mouse fibroblast LM cells enhanced their sensitivity to the cytotoxic effect of eupatoriopicrin. In the clonogenic assay (2 h exposure) 90% cell kill was found with 14.4 μ M eupatoriopicrin in normal cells and 11.7 μ M in cells enriched with arachidonic acid (PUFA cells). After incubation with eupatoriopicrin a more rapid loss of membrane integrity and more lysis was found for PUFA cells in the trypan blue exclusion assay. Using gas chromatography, it was shown that the spectrum of fatty acid acyl chains in the phospholipids of normal cells remained unchanged after 2 h incubation with 20 μ M eupatoripicrin, followed by 24 h post‐incubation. In PUFA cells the polyunsaturated fatty acids were found to degrade possibly due to lipid peroxidation. Using the alkaline unwinding assay and clamped homogeneous electric field electrophoresis, more DNA damage was found in PUFA cells than in normal cells after treatment with eupatoriopicrin. However, because in normal cells, in which PUFA were nearly absent, DNA damage was found as well, it is concluded that lipid peroxidation plays at most a minor role in eupatoriopicrin‐induced cell killing.