Simonart T, Degraef C, Andrei G, Mosselmans R, Hermans P, Van Vooren J P, Noel J C, Boelaert J R, Snoeck R, Heenen M
Department of Dermatology, Erasme University Hospital, Brussels, Belgium.
J Invest Dermatol. 2000 Nov;115(5):893-900. doi: 10.1046/j.1523-1747.2000.00119.x.
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.
铁被怀疑与多种人类肿瘤的诱发和/或进展有关。更具体地说，铁可能参与卡波西肉瘤的发病机制，卡波西肉瘤是一种可能起源于血管的肿瘤。本研究旨在调查铁缺乏对卡波西肉瘤的影响。研究了铁螯合剂以及与血清去除相关的铁缺乏对源自卡波西肉瘤的纺锤状细胞、转化的卡波西肉瘤细胞系（卡波西肉瘤Y-1）和内皮细胞（可能是卡波西肉瘤细胞的祖细胞）的影响。去铁胺和地拉罗司是两种化学结构不相关的铁螯合剂，它们诱导了对内皮细胞和卡波西肉瘤细胞生长的时间和浓度依赖性抑制。细胞生长的抑制与Ki-67以及稳定和总增殖细胞核抗原表达的降低有关。细胞周期蛋白D1和p34细胞周期蛋白依赖性激酶4表达的降低进一步证明了对细胞周期G1期进程的抑制。末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记分析、膜联蛋白-V-荧光素流式细胞术和形态学分析表明，铁螯合也诱导了时间和浓度依赖性凋亡。添加外源性铁可阻止这种凋亡效应。通过血清去除在培养基中诱导铁缺乏导致了类似的细胞周期效应，然而，添加外源性铁只能部分逆转这种效应。总之，这些结果表明，铁缺乏抑制卡波西肉瘤细胞及其假定的内皮前体细胞的生长并诱导其凋亡。这表明铁螯合剂可能是治疗卡波西肉瘤的一种潜在治疗方法。
