Iron chelators inhibit the growth and induce the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors.
Iron is suspected to be involved in the induction and/or progression of various human tumors. More particularly, iron may be involved in the pathogenesis of Kaposi's sarcoma, a tumor of probable vascular origin. This study was designed to investigate the effect of iron deprivation on Kaposi's sarcoma. The effects of iron chelators and iron deprivation associated with serum withdrawal were investigated on Kaposi's sarcoma-derived spindle cells, on a transformed Kaposi's sarcoma cell line (Kaposi's sarcoma Y-1) and on endothelial cells, which are the probable progenitors of Kaposi's sarcoma cells. Desferrioxamine and deferiprone, two chemically unrelated iron chelators, induced a time- and concentration-dependent inhibition of endothelial and Kaposi's sarcoma cell growth. The inhibition of cell growth was associated with a decrease in Ki-67 and in both stable and total proliferating cell nuclear antigen expression. Inhibition of the progression through the G1-phase of the cell cycle was further evidenced by decreased expression of cyclin D1 and of p34 cyclin-dependent kinase 4. Terminal deoxynucleotidyl transferase-mediated desoxyuridinetriphosphate nick end labeling assay, flow cytometry with annexin-V-fluorescein and morphologic analysis indicated that iron chelation also induced a time- and concentration-dependent apoptosis. This apoptotic effect was prevented by the addition of exogenous iron. Induction of iron deprivation in the culture medium by serum withdrawal led to similar cell cycle effects, which, however, could only be partly reverted by the addition of exogenous iron. In conclusion, these results show that iron deprivation inhibits the growth and induces the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors. This suggests that iron chelators may represent a potential therapeutic approach for the treatment of Kaposi's sarcoma.
Simonart
T
T
Department of Dermatology, Erasme University Hospital, Brussels, Belgium. simonart@erasme.ulb.ac.be
Degraef
C
C
Andrei
G
G
Mosselmans
R
R
Hermans
P
P
Van Vooren
J P
JP
Noel
J C
JC
Boelaert
J R
JR
Snoeck
R
R
Heenen
M
M
D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D003676:Deferoxamine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007501:Iron / Q000502:physiology; D007502:Iron Chelating Agents / Q000494:pharmacology*; D000090463:Iron Deficiencies; D008833:Microcirculation; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D012514:Sarcoma, Kaposi / Q000473:pathology*
D007502:Iron Chelating Agents; D007501:Iron; D012264:Ribonucleotide Reductases; D003676:Deferoxamine