铁蛋白
血红素
细胞毒性
癌细胞
博莱霉素
血红素
化学
溶血
孵化
血红蛋白
过氧化氢
癌症研究
分子生物学
生物化学
药理学
免疫学
生物
化疗
癌症
内科学
医学
体外
酶
作者
Jaroslav Čermák,József Balla,Harry S. Jacob,György Balla,H Enright,Karl A. Nath,Gregory M. Vercellotti
出处
期刊:PubMed
日期:1993-11-01
卷期号:53 (21): 5308-13
被引量:33
摘要
Neovascularization and hemorrhage are common features of malignant tumors. We wondered whether hemoglobin derived from extravasated RBC deposits heme-derived iron into the tumor, which could modulate the sensitivity of cancer cells to oxidant-mediated injury. A brief exposure (1 h) of 51Cr-radiolabeled breast cancer cells (BT-20) but not colon cancer cells (Caco-2) to hemin (10 microM) or FeSO4 (10 microM) significantly enhances cytotoxicity mediated by 0.5 mM hydrogen peroxide (H2O2). Associated with Caco-2 resistance, these cells were found to be enriched in the endogenous iron chelator, ferritin. If cellular ferritin is even further increased through 1 h incubation (24 h prior to H2O2 exposure) of both cell types with hemin, FeSO4, or exogenous spleen apoferritin itself (24 h), marked resistance to H2O2-mediated cytotoxicity is manifest. Under several conditions, the sensitivity of tumor cells to oxidant-mediated lysis is inversely proportional to their ferritin content. Pretreatment of BT-20 and Caco-2 cells with hemin or FeSO4 rapidly increases H-ferritin mRNA but only slightly increases L-ferritin mRNA; nevertheless, large increases in overall ferritin content of iron-exposed cells result. Data analogous to those with H2O2-mediated cytotoxicity were obtained in studies of bleomycin-engendered DNA strand breakage and cell damage, i.e., brief treatment of BT-20 cells with both hemin or FeSO4 significantly increases their sensitivity to bleomycin (100 micrograms/ml), whereas treatment followed by 24 h incubation with media alone significantly protects against bleomycin toxicity. We speculate that acute exposure of tumors to iron (e.g., derived from heme-proteins in hemorrhagic cancerous lesions) may increase sensitivity of some cancer cells, particularly those relatively low in endogenous ferritin, to oxidant-mediated lysis. In contrast, repeated, more chronic, exposure effector cells or chemotherapeutic agents, an effect derived from their increased synthesis and accumulation of the intracellular iron scavenger, ferritin.
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