MULTIPLE EFFECTS OF ANTITUMOR ALKYL-LYSOPHOSPHOLIPID ANALOGS ON THE CYTOSOLIC-FREE CA2-CANCER CELL-LINE( CONCENTRATION IN A NORMAL AND A BREAST)

Synthetic alkyl-lysophospholipids (ALP) are a new class of antitumor a gents which interact with the cell membrane and the intracellular sign al transduction at several sites. We studied the modulation of the int racellular calcium concentration ([Ca++](i)) indllced by two alkylglyc erophosphocholines as well as hexadecylphosphocholine and hexadecylpho phoserine in a nontumorigenic and in a tumorigenic breast cell line. W e found three distinct [Ca++](i)-modulating effects: a transient incre ase, a decrease and a sustained increase. Their relative contribution to the observed response varies with different cell types, with the pr oliferation state, with the structure and with the concentration of th e ALP analogs. The transient as well as the sustained increase in [Ca+](i) depend mainly on extracellular Ca++; however, the Ca++ influx-in ducing pathways might be different. The multiple [Ca++](i)-increasing and decreasing effects induced by ALP analogs are discussed in relatio n to their influence on numerous Ca++-dependent effects, e.g. prolifer ation differentiation, apoptosis and cytotoxicity.