In vitro antiproliferative activity of combinations of ether lipid analogues and DNA-interactive agents against human tumor cells

Ether lipid analogues of platelet-activating factor (1-octadecyl-2-acetyl-sn-glycero-3-phosphocholine) possess a wide range of biological activities, including inhibition of neoplastic cell growth in vitro and in vivo. This activity is believed to be membrane mediated. Three different ether lipid an...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1988-04, Vol.48 (7), p.1788-1791
Main Authors: NOSEDA, A, BERENS, M. E, GAINES WHITE, J, MODEST, E. J
Format: Article
Language:English
Subjects:
Adenocarcinoma
Antineoplastic agents
Antineoplastic Agents - administration & dosage
Antineoplastic Combined Chemotherapy Protocols
Biological and medical sciences
Cell Division - drug effects
Cell Survival - drug effects
Cisplatin - administration & dosage
Cyclophosphamide - administration & dosage
Cyclophosphamide - analogs & derivatives
Doxorubicin - administration & dosage
Female
General aspects
In Vitro Techniques
Medical sciences
Ovarian Neoplasms
Pharmacology. Drug treatments
Phospholipid Ethers - pharmacology
Piperidines - pharmacology
Tumor Cells, Cultured
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Summary:Ether lipid analogues of platelet-activating factor (1-octadecyl-2-acetyl-sn-glycero-3-phosphocholine) possess a wide range of biological activities, including inhibition of neoplastic cell growth in vitro and in vivo. This activity is believed to be membrane mediated. Three different ether lipid analogues, 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine, 1-thiohexadecyl-2-ethyl-rac-glycero-3-phosphocholine, and 4-amino-methyl-1-[2,3-(di-n-decyloxy)-n-propyl]-4-phenylpiperidine , were combined with three DNA-interactive drugs, Adriamycin, 4-hydroperoxycyclophosphamide, and cisplatin, in the expectation that combinations of drugs with different mechanisms of action might show enhanced antitumor activity. The in vitro antiproliferative activity of the combinations was measured with a semisoft agarose clonogenic assay of an ovarian adenocarcinoma cell line. Various permutations of drug combinations were studied. Isobologram analyses and different treatment schedules were performed. Enhanced antiproliferative activity was found with combinations of ether lipids with DNA-interactive drugs in comparison with single agents. Statistical evaluation of the data indicated that the increase in activity was due to an additivity phenomenon. Neither synergism nor antagonism was found.
ISSN:0008-5472
1538-7445