Uptake of anti-anemic substance ferric-sorbitol-citrate by normal and malignant cells and its effects on expression of transferrin receptor 1 and ferritin
| Autor: | Maja Prutki, Visnja Orescanin, Neven Zarkovic, Branka Mihaljević, Marija Poljak-Blazi |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Lipid Peroxides Iron Gene Expression Transferrin receptor ferric-sorbitol-citrate iron metabolism transferrin receptor 1 ferritin lipid peroxidation carcinoma cells Biology Ferric Compounds Proto-Oncogene Mas Cell Line Antigen In vivo Antigens CD Neoplasms Receptors Transferrin Humans Radiology Nuclear Medicine and imaging Citrates Pharmacology chemistry.chemical_classification Anemia General Medicine Molecular biology In vitro Culture Media Ferritin Oncology Biochemistry chemistry Transferrin Cell culture Apoptosis Ferritins biology.protein Lipid Peroxidation |
| Popis: | Iron-containing antianemic drug ferric-sorbitol-citrate (FSC) inhibits the proliferation of various cancer cell lines in vitro and causes a regression of experimental murine tumors in vivo but does not affect the proliferation of nonmalignant cells. Growth modification caused by FSC iron involves a diminished expression of Bcl-2 and an overexpression of p53 proto-oncogene, accompanied by an increased incidence of apoptosis. Aiming to evaluate further the activity principle of the anticancer effects of this antianemic drug, in this study, we analyzed the utilization of iron from FSC and the effects of FSC iron on transferrin receptor 1 (TfR1) and ferritin expression. Without FSC iron, all the cell lines had an equal expression of TfR1, but if cultured in FSC-supplemented medium, human colon SW620 and laryngeal carcinoma Hep cells exhibited a lower expression of TfR1-positive cells than nonmalignant Wi38 fibroblasts and pancreatic carcinoma MiaPaCa2 cells. The most sensitive to FSC iron were colon carcinoma SW620 cells, whereas Wi38 fibroblasts were not sensitive at all. Increased iron uptake by colon carcinoma cells was noticed in the first 3 hours of the incubation with FSC iron, whereas higher FSC iron concentrations and longer incubation also impaired ferritin expression in SW260 colon carcinoma cells. Thus, the anticancer ability of FSC could result from its higher initial utilization of iron and consecutive negative signal for the expression of TfR1 in tumor cells. Tumor cells containing lower amounts of ferritin are probably more sensitive to oxidative stress caused by iron overload, whereas FSC iron itself was proven to be chemically stable and did not induce lipid peroxidation. |
| Databáze: | OpenAIRE |
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