In order to screen new differentiation-inducing compounds which were expected to be anti-cancer drugs without cytotoxicity in normal cell, we extracted natural compounds from ma-rine organisms and screened the differentiation-inducing activity using F9 teratocarcinoma cell as an assay system. Previously, we reported that HA-3 fraction from the sea cucumber Sfichopus japonicus and ME-B from the marine mollusk mytilus edulis show differentiation-in-ducing activities on F9 cells. In this study, these fractions were further purified on the basis of the tumor cell differentiation-inducing activity of these Purified marine natural compounds. Galactose-isoleucine mixture of S.japonicus HA-3-5 and sphingosine fraction of M. edulis, ME-Bu-9d are more effective than others on tumor cell differentiation via induction of morphologi-cal changes and regulation of the expression of laminin, type IV collagen and retinoic acid re-ceptor β, differentiation-specific genes, in F9 cells, Moreover, these compounds effectively sup-pressed the tumor cell growth without cytotoxicity. Thus, present results suggest that HA-3-5and ME-Bu-9d fraction have the F9 cell differentiation-inducing activity, which may be medi-ated through the regulation of specific genes such as laminin, type TV collagen and retinoic acid receptor β.

Keywords: Differentiation,F9 cell, Marine natural compounds