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Oncogene activation and apoptosis as possible mechanism of antitumour effect of ferric-sorbitol-citrate

The complex mechanism of Jectofer influence on cell proliferation is not entirely understood. For a better understanding of the mechanism of drug action, DNA fragmentation in control and treated CaCo2 (colon carcinoma) cells was analised by 1.5% agarose gel electrofores. Influence of iron from FSC, on the expression of c-myc, Bcl-2, and wild and mutant p53 protein was also examined. After treatment, for 72 hours, with ferric sorbitol citrate (FSC) we obserwed impaired viability of three carcinoma (Ca) cell line ; CaCo2 (colon Ca), MiaPaCa2 (pancreatic Ca) and Hela (cervics Ca), measured by MTT assay. The most pronounced growth inhibitory effect was observed on MiaPaCa and CaCo2 cells. After treatment with two higher doses of FSC (10-4 to 10-3 M), about 70 % of viable cells left. In spite of that, all concentrations of FSC stimulated the proliferation of non malignant HEF522 (human embrionic fibroblasts) cells. Intensity of apoptotic processes was greater in treated cells than in non treated CaCo2 cells. The degree of DNA fragmentation followed the morphological changes and the growth inhibition of the investigated cells. Growth modification of CaCo2 cells caused by FSC involves interference with the diminished expression of Bcl-2, and an over expression of mp53 oncogene. Expression of c-my and wp53 protein was not altered after tretment with FSC. Thus, the specific antitumour effect of FSC involves DNA damage, oncogene alteration, and apoptosis. The mechanism of FSC-activity might result in dual activity of this iron containing drug: inhibition of malignant cell proliferation and induction of apoptosis.

Jectofer; tumour cell proliferation; apoptosis; oncogenes

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