Modulation of the cytosolic Ca + + concentration by alkylphospho- l-serine analogs: relation to their antiproliferative action

Antiproliferative alkyllysophospholipid (ALP) analogs produced multiple effects on the cytosolic Ca + + concentration ([Ca + +] i) in an immortalized human breast epithelial cell line (H 184). The addition of small concentrations resulted in a short transient [Ca + +] i response. With higher concent...

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Bibliographic Details
Published in:Journal of lipid mediators and cell signalling 1997, Vol.15 (2), p.103-114
Main Authors: Bergmanna, Jutta, Junghahn, Ilse, Brachwitz, Hans, Vollgraf, Christine, Langen, Peter
Format: Article
Language:English
Subjects:
Alkylation
Breast - metabolism
Calcium - metabolism
Cell Division - drug effects
Cell Line, Transformed
Cytosol - metabolism
Dose-Response Relationship, Drug
Epithelium - metabolism
Humans
Molecular Structure
Phosphatidylserines - chemistry
Phosphatidylserines - pharmacology
Structure-Activity Relationship
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Summary:Antiproliferative alkyllysophospholipid (ALP) analogs produced multiple effects on the cytosolic Ca + + concentration ([Ca + +] i) in an immortalized human breast epithelial cell line (H 184). The addition of small concentrations resulted in a short transient [Ca + +] i response. With higher concentrations the transient rise was followed by a sustained increase. Pretreatment of cells with the ALP analogs for two minutes inhibited the transient [Ca + +] response. Increases in [Ca + +] i and inhibition of the transient increase were studied in relation to the dose and structure of several ALP analogs. In a series of alkylphospho- l-serine analogs with different lengths of the alkyl chain we found different dependencies of the stimulatory and inhibitory effects on the dose and the structure. The ability to increase [Ca ++ ] i is absent with the C 14 and C 15 analogs, is low with the C 16 and high with the C 18 analog. With the exception of the C 12 analog, a dose-related inhibition was observed with all derivatives but the effective concentrations differed very strongly and the maximal potency was reached with the C 15 and C 16 analogs. The antiproliferative action seems to correlate rather with the potency to inhibit the transient [Ca + +]; response than with its stimulation.
ISSN:0929-7855
DOI:10.1016/S0929-7855(96)00448-8