J. Bergmann et al., MODULATION OF THE CYTOSOLIC CA-L-SERINE ANALOGS - RELATION TO THEIR ANTIPROLIFERATIVE ACTION(+ CONCENTRATION BY ALKYLPHOSPHO), Journal of lipid mediators and cell signalling, 15(2), 1997, pp. 103-114
Antiproliferative alkyllysophospholipid (ALP) analogs produced multipl
e effects on the cytosolic Ca++ concentration ([Ca++](i)) in an immort
alized human breast epithelial cell line (H 184). The addition of smal
l concentrations resulted in a short transient [Ca++](i) response. Wit
h 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 in
hibition of the transient increase were studied in relation to the dos
e and structure of several ALP analogs. In a series of alkylphospho-L-
serine analogs with different lengths of the alkyl chain we found diff
erent dependencies of the stimulatory and inhibitory effects on the do
se 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-1
8 analog. With the exception of the C-12 analog, a dose-related inhibi
tion was observed with all derivatives but the effective concentration
s 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++](i) response t
han with its stimulation.