Document Detail

Cytotoxic interactions of heat and an ether lipid analogue in human ovarian carcinoma cells.
MedLine Citation:
PMID:  2804975     Owner:  NLM     Status:  MEDLINE    
Ether lipid (EL) analogues of platelet activating factor are known to have a cell membrane-mediated antitumor activity. Although previous studies demonstrated additive interactions with EL and conventional DNA-interacting chemotherapeutic agents, little is known about the interaction of EL with heat. In this study, the cytotoxic interaction of one EL analogue, ET-18-OMe, with heat was measured at two different temperatures, 42 and 44 degrees C, using BG-1 human ovarian carcinoma cells. When the number of colonies, greater than or equal to 40 microns in diameter, was counted as a function of incubation time, the rate of colony formation was suppressed by treatment with ET-18-OMe alone at doses greater than or equal to 2.0 microM or with heat alone. The combination of ET-18-OMe with heat inhibited the colony formation of the slowest growing fraction of the heated cells. The dose-response curve for BG-1 cells after continuous exposure to ET-18-OMe alone was exponential with a small shoulder (Dq = 0.25 microM). The T0 value (the time to reduce survival on the exponential portion of the curve by a factor of 1/e) of the 44 degrees C dose-response curve (30 min) was reduced to half (15 min) by the addition of 0.25 to 1.0 microM ET-18-OMe, but increased again to 24 min when heat was combined with ET-18-OMe concentrations greater than or equal to 2.0 microM. The thermotolerant tail seen in the dose-response curve after continuous heating at 42 degrees C was removed by adding as little as 0.25 microM ET-18-OMe. Isobologram analysis for the combined treatments with 44 degrees C heat and ET-18-OMe at surviving fractions of 0.5, 0.3, 0.1, and 0.01 showed that the treatments were supraadditive at low concentrations (less than 0.5 microM) of ET-18-OMe and additive at moderate concentrations (0.5 to 1.0 microM) of ET-18-OMe. Similarly, the interaction of ET-18-OMe with 42 degrees C heat at surviving fractions of 0.3 and 0.1 was supraadditive at low concentrations (less than 0.5 microM) of the ET-18-OMe and additive with moderate concentrations (0.5 to 1.5 microM) of ET-18-OMe. Because the greatest interaction of ET-18-OMe and heat occurred at clinically achievable doses of both agents, this combination of agents should be considered for use in clinical trials.
K Fujiwara; E J Modest; C E Welander; C A Wallen
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  49     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1989 Nov 
Date Detail:
Created Date:  1989-12-11     Completed Date:  1989-12-11     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  6285-9     Citation Subset:  IM    
Department of Radiology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27103.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Cell Line
Cell Survival* / drug effects
Dose-Response Relationship, Drug
Hot Temperature*
Ovarian Neoplasms
Phospholipid Ethers / pharmacology*
Tumor Cells, Cultured / cytology*,  drug effects
Tumor Stem Cell Assay
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents; 0/Phospholipid Ethers; 65492-82-2/edelfosine

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