An immunosuppressive agent, FTY720, increases intracellular concentration of calcium ion and induces apoptosis in HL-60

Immunology. 1997 Aug;91(4):594-600. doi: 10.1046/j.1365-2567.1997.d01-2281.x.


We previously reported that FTY720 is an efficient inducer of apoptosis in lymphocytes and cultured cell lines. In the present study, HL-60 human promyerocytoma cells also induced apoptosis through in vitro treatment with the drug, demonstrating extensive DNA fragmentation 6 hr after incubation. The major target of FTY720 was the common signalling pathway of apoptosis, since a rapid (< 1 min) increase in the intracellular Ca2+ concentration ([Ca2+]i) was found in the cells treated with the drug. Calcium chelation in the culture medium with EGTA did not affect the [Ca2+]i mobilization. A phospholipase C inhibitor, U73122, inhibited the increase in [Ca2+]i as well as the fragmentation of the nuclear DNA, whereas U73343, a non-effective analogue of U73122, had little effect. These results suggest that FTY720-induced apoptosis is mediated through an activation of phospholipase C and the subsequent release of Ca2+ from intracellular calcium pools. In addition, the treatment of HL-60 with pertussis toxin (PTX) did not inhibit Ca2+ mobilization or apoptosis, suggesting that the activation of phospholipase C is independent of PTX-sensitive G-proteins.

MeSH terms

  • Apoptosis / drug effects*
  • Calcium / metabolism*
  • DNA Fragmentation / drug effects
  • Estrenes / pharmacology
  • Fingolimod Hydrochloride
  • HL-60 Cells
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Pertussis Toxin
  • Phosphodiesterase Inhibitors / pharmacology
  • Propylene Glycols / pharmacology*
  • Pyrrolidinones / pharmacology
  • Sphingosine / analogs & derivatives
  • Type C Phospholipases / physiology
  • Virulence Factors, Bordetella / pharmacology


  • Estrenes
  • Immunosuppressive Agents
  • Phosphodiesterase Inhibitors
  • Propylene Glycols
  • Pyrrolidinones
  • Virulence Factors, Bordetella
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Pertussis Toxin
  • Type C Phospholipases
  • Fingolimod Hydrochloride
  • Sphingosine
  • Calcium