This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fujiwara, K. Articles by Wallen, C. A. Search for Related Content PubMed PubMed Citation Articles by Fujiwara, K. Articles by Wallen, C. A.

Cytotoxic Interactions of Heat and an Ether Lipid Analogue in Human Ovarian Carcinoma Cells¹

Departments of Radiology [K. F., C. A. W.], Biochemistry [E. J. M.], and Obstetrics and Gynecology [C. E. W.], Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27103

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°C, using BG-1 human ovarian carcinoma cells. When the number of colonies, 40 µm 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 2.0 µM 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 (D_q = 0.25 µM). The T₀ value (the time to reduce survival on the exponential portion of the curve by a factor of 1/e) of the 44°C dose-response curve (30 min) was reduced to half (15 min) by the addition of 0.25 to 1.0 µM ET-18-OMe, but increased again to 24 min when heat was combined with ET-18-OMe concentrations 2.0 µM. The thermotolerant tail seen in the dose-response curve after continuous heating at 42°C was removed by adding as little as 0.25 µM ET-18-OMe. Isobologram analysis for the combined treatments with 44°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 (<0.5 µM) of ET-18-OMe and additive at moderate concentrations (0.5 to 1.0 µM) of ET-18-OMe. Similarly, the interaction of ET-18-OMe with 42°C heat at surviving fractions of 0.3 and 0.1 was supraadditive at low concentrations (<0.5 µM) of the ET-18-OMe and additive with moderate concentrations (0.5 to 1.5 µM) 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.

¹ Supported by NIH Grant CA 44105 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Department of Radiology, Bowman Gray School of Medicine, 300 South Hawthorne Road, Winston-Salem, NC 27103.

Received 5/16/89. Revised 8/15/89. Accepted 8/22/89.