Effects of hexadecylphosphocholine on thrombocytopoiesis.
Hexadecylphosphocholine (HePC) is the first representative of the alkylphosphocholines, a novel group derived from the cytotoxic etherlysophospholipids. HePC shows a broad spectrum of antiproliferative effects in neoplastic cells in vitro and in vivo. HePC has been tested successfully in several clinical studies. One of the remarkable features of this compound has been the induction of a leucocytosis and a thrombocytosis in most of the patients receiving HePC systemically. In this paper, we have investigated the biological and molecular mechanisms by which HePC exerts this interesting effect. We found that HePC acts as an unspecific costimulator on human megakaryocytic proliferation in a soft agar assay system predominantly together with thrombopoietin (TPO). Furthermore, HePC leads to the synthesis and secretion of several haematopoietic growth factors in monocytes and bone marrow fibroblasts, determined by the direct measurement of growth factors in cellular supernatants and by the measurement of growth factor mRNA in cell extracts. Thus, HePC seems to produce the increase of blood platelets in tumour patients by two different mechanisms.
Berkovic
D
D
University Clinic of Göttingen, Department of Internal Medicine, Göttingen, Germany.
Bensch
M
M
Bertram
J
J
Wille
T
T
Haase
D
D
Binder
C
C
Fleer
E A
EA
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D002455:Cell Division; D004797:Enzyme-Linked Immunosorbent Assay; D016298:Hematopoietic Cell Growth Factors / Q000096:biosynthesis*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008533:Megakaryocytes / Q000187:drug effects / Q000473:pathology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D013922:Thrombocytosis / Q000139:chemically induced / Q000473:pathology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016298:Hematopoietic Cell Growth Factors; D012333:RNA, Messenger; D010767:Phosphorylcholine; C039128:miltefosine