Naslov
Uptake of anti-anemic substance ferric-sorbitol-citrate by normal and malignant cells and its effects on expression of transferrin receptor 1 and ferritin

Autori
Prutki, Maja ; Poljak-Blaži, Marija ; Mihaljević, Branka ; Oreščanin, Višnja ; Žarković, Neven

Izvornik
Cancer Biotherapy & Radipharmaceuticals (1084-9785) 21 (2006), 6; 636-644

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
ferric-sorbitol-citrate; iron metabolism; transferrin receptor 1; ferritin; lipid peroxidation; carcinoma cells

Sažetak
Iron containing anti anemic drug ferric-sorbitol-citrate (FSC) inhibits proliferation of various cancer cell lines in vitro and causes regression of experimental murine tumors in vivo, but does not affect proliferation of non-malignant cells. Growth modification caused by FSC iron involves diminished expression of Bcl-2, and over-expression of p53 proto oncogene, accompanied by increased incidence of apoptosis. Aiming to evaluate further activity principle of the anticancer effects of this anti-anemic drug in this study we analyzed 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 equal expression of TfR1, but if cultured in FSC-supplemented medium, human colon SW620 and laryngeal carcinoma Hep cells exhibited lower expression of TfR1 positive cells than non-malignant Wi38 fibroblasts and pancreatic carcinoma MiaPaCa2 cells. The most sensitive to FSC iron were colon carcinoma SW620 cells, while 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, while higher FSC iron concentrations and longer incubation impaired also ferritin expression in SW260 colon carcinoma cells. Thus, the anticancer ability of FSC could result from 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, while FSC iron itself was proven to be chemically stable and did not induce lipid peroxidation.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti, Kliničke medicinske znanosti

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