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 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 C14 and C15 analogs, is low with the C16 and high with the C18 analog. With the exception of the C12 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 C15 and C16 analogs. The antiproliferative action seems to correlate rather with the potency to inhibit the transient [Ca++]i response than with its stimulation.