Stimulation of human hematopoietic progenitor cells by the alkylphosphocholines hexadecylphosphocholine and hexadecyl-N,N,N-trimethyl-hexanolamine

Anticancer Res. 1999 Jul-Aug;19(4B):3213-9.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Division / drug effects
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Interleukin-3 / pharmacology
  • Middle Aged
  • Phosphorylcholine / analogs & derivatives
  • Phosphorylcholine / pharmacology*

Substances

  • Interleukin-3
  • Phosphorylcholine
  • Granulocyte Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor