Synergistic cytotoxic effects of ether phospholipid analogues and ionizing radiation in human carcinoma cells.
OBJECTIVE
There is growing evidence in recent years that the antiproliferative effects of ionizing radiation may not be exclusively mediated via DNA damage but also by interactions and alterations of cell membrane associated processes. Here, we tested the hypothesis that membrane active cytotoxic ether lipids and analogues may interact with ionizing radiation, enhancing its antiproliferative effects.


METHODS
The two epithelial tumor cell lines HTB 43 and KB, and the ether lipid resistant subline KBr were treated by a combination of radiation and ether lipids. Cytotoxic effects were measured by colony forming assays and the effects on membrane phospholipids were determined by quantitative thin-layer chromatography of cell lipid extracts.


RESULTS
We present evidence that some ether lipids show supra-additive cytotoxic effects with ionizing radiation. These effects seem to depend on the same structural properties of ether lipids that determine their intrinsic cytostatic and cytotoxic activity. Identical growth inhibitory results were achieved when cells were treated before, or 30 min after irradiation. Analysis of major membrane phospholipids revealed no statistically significant differences of phospholipid distribution pattern in cells exposed to both treatment modalities.


CONCLUSIONS
Our data indicate that changes of overall membrane phospholipid composition do not seem to be the mechanism of synergistic antiproliferative activity of ether lipids and ionizing radiation.
Berkovic
D
D
Department of Hematology and Oncology, University Clinic of Göttingen,Germany.
Gründel
O
O
Berkovic
K
K
Wildfang
I
I
Hess
C F
CF
Schmoll
H J
HJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D003131:Combined Modality Therapy; D004357:Drug Synergism; D006801:Humans; D007624:KB Cells; D008563:Membrane Lipids / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008563:Membrane Lipids; D010742:Phospholipid Ethers; D010743:Phospholipids