SELECTIVE-INHIBITION OF CELL-PROLIFERATION AND DNA-SYNTHESIS BY THE POLYSULFATED CARBOHYDRATE IOTA-CARRAGEENAN

HOFFMAN, R and BURNS, WW and PAPER, DH (1995) SELECTIVE-INHIBITION OF CELL-PROLIFERATION AND DNA-SYNTHESIS BY THE POLYSULFATED CARBOHYDRATE IOTA-CARRAGEENAN. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 36 (4). pp. 325-334. ISSN 0344-5704,

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Abstract

iota-Carrageenan is a polysulphated carbohydrate that antagonises some heparin-binding growth factors. We assessed the effect of iota-carrageenan on the proliferation of a panel of cell lines, some of which require heparin-binding growth factors for mitogenesis. The importance of growth factor antagonism for the antiproliferative activity was also determined. Cell proliferation was determined by cell counts and a tetrazolium dye (MTT) assay, and DNA synthesis was determined by thymidine incorporation. The proliferation of the basic fibroblast growth factor (bFGF)-dependent endothelial cell line FBHE was inhibited by daily administration of iota-carrageenan in a dose-dependent manner [concentration inhibiting cell growth by 50% (IC50 value), approx. 0.5 mu g/ml]. However, excess bFGF did not reverse the inhibitory effect. DNA synthesis was completely inhibited by concentrations of l-carrageenan that nonetheless allowed significant protein synthesis to occur. The proliferation of the androgen-dependent prostate-carcinoma cell line LNCaP was also inhibited by iota-carrageenan (IC50 value, 5.5 mu g/ml) and the cells were arrested at the G1/S boundary. iota-Carrageenan inhibited DNA synthesis in MCF-7 cells stimulated by bFGF and transforming growth factor alpha (TGF alpha) but not in those stimulated by insulinlike growth factor 1 (IGF-1). Blocking IGF-1-mediated DNA synthesis with anti-IGF-1 receptor antibody alpha IR3 enhanced the inhibitory activity of iota-carrageenan against MCF-7 cells grown in serum. A number of other transformed and non-transformed cell lines were either partially inhibited or not inhibited by iota-carrageenan. iota-Carrageenan had low anti-coagulant activity. iota-Carrageenan is a selective anti-proliferative agent and warrants further investigation for anti-angiogenic therapy (in view of its activity against endothelial cells) and for the treatment of androgen-dependent prostate cancer.

Item Type: Article
Uncontrolled Keywords: FIBROBLAST GROWTH-FACTOR; TUMOR-GROWTH; PENTOSAN POLYSULFATE; SULFATED POLYSACCHARIDES; HEPARAN-SULFATE; FACTOR BINDING; CANCER CELLS; OVEREXPRESSION; ANGIOGENESIS; RECEPTORS; IOTA-CARRAGEENAN; GROWTH FACTORS
Depositing User: Dr. Gernot Deinzer
Last Modified: 19 Oct 2022 08:37
URI: https://pred.uni-regensburg.de/id/eprint/52393

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