N-all-trans-retinoyl-L-proline inhibits metastatic potential of hepatocellular carcinoma cells.

Abstract	Tumor metastasis is usually a serious problem in tumor patients because of the lack of therapeutic approaches. A new compound, N-all-trans-retinoyl-L-proline (ATRP), has been developed and its metastasis inhibition activity has been studied. Low concentrations of ATRP have already been found to inhibit hepatocellular carcinoma cells (HCC) in a dose- and time-dependent manner by inducing the expression of p27(kip). We found that ATRP inhibited metastasis-associated behaviors in Hep3B cells, such as cell migration, invasion, collagen adhesion and gelatinase expression, more significantly than retinoic acid. Further, such inhibitory activities were observed in the regulation of cellular surface fucosylated epitope functions, such as binding of ulex europaeus lectin, expression of Lewis x, y and b, and activity of alpha1,3 fucosyltransferase. Hep3B cells pretreated with ATRP showed a significantly reduced incidence of experimental intrahepatic metastasis in nude mice. We conclude that ATRP is an alternative inhibitor and potential therapeutic agent for HCC metastasis with a different mechanism of action from ATRP.
Authors	Xing Zhong Wu, Peng-Chen Shi, Ping Hu, Yi Chen, Sheng-Song Ding
Journal	Cell biology international (Cell Biol Int) Vol. 30 Issue 8 Pg. 672-80 (Aug 2006) ISSN: 1065-6995 [Print] England
PMID	16806999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents N-retinoylproline Receptors, Retinoic Acid Fenretinide Fucose Tretinoin Proline Fucosyltransferases Gelatinases
Topics	Animals Antineoplastic Agents (chemistry, pharmacology, therapeutic use) Carcinoma, Hepatocellular (drug therapy, pathology) Cell Adhesion (drug effects) Cell Cycle (drug effects) Cell Movement (drug effects) Fenretinide (chemistry) Fucose (metabolism) Fucosyltransferases (metabolism) Gelatinases (antagonists & inhibitors) Humans Liver Neoplasms, Experimental (drug therapy, pathology) Mice Mice, Nude Molecular Structure Neoplasm Invasiveness Neoplasm Transplantation Proline (analogs & derivatives, chemistry, pharmacology, therapeutic use) Receptors, Retinoic Acid (metabolism) Tretinoin (analogs & derivatives, chemistry, pharmacology, therapeutic use) Tumor Cells, Cultured

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