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 var ious human tumors. More particularly, iron may be involved in the pathogene sis of Kaposi's sarcoma, a tumor of probable vascular origin. This study wa s designed to investigate the effect of iron deprivation on Kaposi's sarcom a. 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 end othelial cells, which are the probable progenitors of Kaposi's sarcoma cell s. 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 n uclear antigen expression. Inhibition of the progression through the G(1)-p hase of the cell cycle was further evidenced by decreased expression of cyc lin D1 and of p34 cyclin-dependent kinase 4. Terminal deoxynucleotidyl tran sferase-mediated desoxyuridinetriphosphate nick end labeling assay, flow cy tometry 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. Indu ction of iron deprivation in the culture medium by serum withdrawal led to similar cell cycle effects, which, however, could only be partly reverted b y the addition of exogenous iron. In conclusion, these results show that ir on deprivation inhibits the growth and induces the apoptosis of Kaposi's sa rcoma cells and of their putative endothelial precursors. This suggests tha t iron chelators may represent a potential therapeutic approach for the tre atment of Kaposi's sarcoma.