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 an titumoral compounds, the alkylphosphocholines. In vivo studies of HePC show ed an inn ease in the total white blood count (WBC) in the highest dosage g roup in DMBA-induced breast carcinoma in the rat. In phase II studies most of 70 patients treated orally with HePC likewise showed a significant incre ase 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 s elective co-stimulatory effect of HePC on the G-CSF-dependent growth of bon e marrow progenitor cells in progenitor cells from 22 patients Hexadecyl-N, N,N-trimethyl-hexanolamine (HePC6), which has no, or only marginal antitumo ral activity brit comparable physicochemical properties to HePC, also stimu lates 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-depende nt colony formation is not entirely understood. An inhibitory effect of HeP C and ether lipids on protein kinase C (PKC) has been described. However; t here also is evidence that etherlipids can stimulate PKC, which plays a cru cial role in proliferation and survival of hematopoietic cells, under more physiological conditions. Therefore, the most likely explanation for the st imulating effect of HePC on G-CSF-dependent colony formation might be inter ference with signal transduction pathways.