Induction of hepatocyte growth factor and inhibition of proliferation by extracellular matrix component derived from fish skin of Reinhararditus hippoglossoides

The skin of halibut Reinhararditus hippoglossoides has been discarded as a waste product in large quantities by the food industry; hence, we examined the biological activity in the skin in order to make good use of the waste. In the present study, we determined induction of hepatocyte growth factor (HGF) from the MRC-5 human fibroblast cells and inhibition of cell proliferation in tumor cells using various components extracted from the fish skin. The glycosaminoglycan fraction was extracted with alkali solution and fractionated by ion chromatography. Consequently, dermatan sulfate showed the strongest activity in HGF induction, as well as commercially available heparin and heparan sulfate. Moreover, the alkali extract of fish skin showed inhibition of proliferation for some tumor cells in vitro. In particular, viable cells determined by 3-(4,5-dimethyl-2-thiazolyi)-2,5-diphenyltetrazolium bromide (MTT) assay were significantly decreased by 5% in HL60 and 8% in U937 of leukemia cells in the medium containing 5 mg/mL alkali extract. These observations indicate that the fish skin has significant biological activity and is valuable for functional foods and drugs.