Involvement of lipid peroxidation, oncogene expression and induction of apoptosis in the antitumorous activity of ferric-sorbitol-citrate

We described before that iron-containing, anti-anaemic drug, ferric-sorbito l-citrate complex (FSC) inhibited proliferation of various murine cancer ce lls in vitro and caused tumour regression in vivo, but did nor affect proli feration of the non-malignant cells. The aim of this study was to evaluate further the anticancer activity mechanism of FSC using human colon cancer c ell line CaCo2. After treatment with FSC for 72 hours impaired proliferativ e ability and viability of CaCo2 cells as observed. Growth modification cau sed by FSC involved diminished expression of Bcl-2, and over-expression of mp53 proto-oncogenes, accompanied by increased incidence of apoptosis. Immu nostaining the cells applying monoclonal antibodies for lipid peroxidation product 4-hydroxynonenal (HNE) showed that FSC-iron increased intracellular HNE, but did not induce severe HNE-mediated oxidative stress. Thus, antitu morous mechanism of FSC involves modulation of oncogene expression and indu ction of apoptosis apparently not triggered by lipid peroxidation-mediated oxidative stress, although FSC might restore endogenous HNE production in t he CaCo2 cells to level resembling physiological for various non-malignant cells and tissues. Higher dose of FSC increased also number of intracellula r ferritin positive CaCo2 cells.