Antiproliferative effect and interaction of fucans with cells

Abstract

Fucans were extracted from the brown seaweed Ascophyllum nodosum, degraded by acidic hydrolysis, fractionated by gel nitration and characterized by high performance steric exclusion chromatography. Different fucan fractions of average molecular weight 6000–150000 g mol −1 were thus obtained. The effects of these low molecular weight (LMW) fucans on cells were examined. The results show that these fucans can inhibit the growth of some cell lines. The Chinese hamster fibroblasts (CCL 39) are strongly inhibited, without any cytotoxicity, showing an inhibition percentage of 80% at a fucan concentration of 1000 μg ml −1, while inhibition does not exceed 50% on human colon adenocarcinoma cells (COLO 320DM) at the same fucan concentration. Other tumor cell lines examined here are not sensitive to these fucans (human mammary tumor cell line MCF7, murine leukemic cells P388 and human fibroblasts McCoy). This fucan inhibitory effect seems to be dependent on the sulfate group content. We show that no fucan molecular weight effect was observed for fractions in the range 10000–150000 g mol −1. However, the fucan fractions with a molecular weight under 10000 g mol −1 are less active. The analysis of the cells by flow cytometry shows that fucans did not induce any perturbations on the cell distribution in the various phases of the cell cycle, but they did influence the synthesis and secretion of thrombospondin. On human fibroblasts (McCoy), no antiproliferative effect was observed, but it seems that fucans led to substantial alterations of cell adhesion without any cytotoxicity. More information concerning the fucan mechanism is necessary to understand how they interact with the extracellular matrix.