Stimulation of human hematopoietic progenitor cells by the alkylphosphocholines hexadecylphosphocholine and hexadecyl-N,N,N-trimethyl-hexanolamine.
Hexadecylphosphocholine (HePC) represents a new class of membrane-active antitumoral compounds, the alkylphosphocholines. In vivo studies of HePC showed an increase in the total white blood count (WBC) in the highest dosage group in DMBA-induced breast carcinoma in the rat. In phase II studies most of 70 patients treated orally with HePC likewise showed a significant increase in WBC and a rise in platelet count. The present investigation on human bone marrow progenitor cells from 42 patients shows a dose-dependent and selective co-stimulatory effect of HePC on the G-CSF-dependent growth of bone marrow progenitor cells in progenitor cells from 22 patients. Hexadecyl-N,N,N-trimethyl-hexanolamine(HePC6), which has no, or only marginal antitumoral activity but comparable physicochemical properties to HePC, also stimulates the G-CSF-dependent colony formation in a dose-dependent manner. The molecular mode of action of the stimulating effect of HePC on G-CSF-dependent colony formation is not entirely understood. An inhibitory effect of HePC and ether lipids on protein kinase C (PKC) has been described. However, there also is evidence that etherlipids can stimulate PKC, which plays a crucial role in proliferation and survival of hematopoietic cells, under more physiological conditions. Therefore, the most likely explanation for the stimulating effect of HePC on G-CSF-dependent colony formation might be interference with signal transduction pathways.
Ergezinger
K
K
Department of Pediatrics, University Hospital Würzburg, Germany.
Vehmeyer
K
K
Unger
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008875:Middle Aged; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology*
D007377:Interleukin-3; D010767:Phosphorylcholine; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor