Multiple effects of antitumor alkyl-lysophospholipid analogs on the cytosolic free Ca2+ concentration in a normal and a breast cancer cell line.
Synthetic alkyl-lysophospholipids (ALP) are a new class of antitumor agents which interact with the cell membrane and the intracellular signal transduction at several sites. We studied the modulation of the intracellular calcium concentration ([Ca++]i) induced by two alkylglycerophosphocholines as well as hexadecylphosphocholine and hexadecylphosphoserine in a nontumorigenic and in a tumorigenic breast cell line. We found three distinct [Ca++]i-modulating effects: a transient increase, a decrease and a sustained increase. Their relative contribution to the observed response varies with different cell types, with the proliferation state, with the structure and with the concentration of the ALP analogs. The transient as well as the sustained increase in [Ca++]i depend mainly on extracellular Ca++; however, the Ca++ influx-inducing pathways might be different. The multiple [Ca++]i-increasing and decreasing effects induced by ALP analogs are discussed in relation to their influence on numerous Ca(++)-dependent effects, e.g. proliferation, differentiation, apoptosis and cytotoxicity.
Department of Hematology and Oncology, Klinikum Steglitz, Freie Universität Berlin, Germany.
J
J
Bergmann
I
I
Junghahn
H
H
Brachwitz
P
P
Langen
D000478:Alkylation; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008246:Lysophospholipids / Q000494:pharmacology*; D010742:Phospholipid Ethers / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D010768:Phosphoserine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction; D013329:Structure-Activity Relationship
C090562:2-chloro-2-deoxy-1-O-hexadecylglycero-3-phosphocholine; D000970:Antineoplastic Agents; D008246:Lysophospholipids; D010742:Phospholipid Ethers; D010767:Phosphorylcholine; C090561:hexadecylphosphoserine; D010768:Phosphoserine; C026659:edelfosine; C039128:miltefosine; D002118:Calcium