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

Abstract 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.