N-all-trans-retinoyl-L-proline inhibits metastatic potential of hepatocellular carcinoma cells.
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.
Wu
Xing Zhong
XZ
Department of Biochemistry, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, PR China. xz_wu@shmu.edu.cn
Shi
Peng-Chen
PC
Hu
Ping
P
Chen
Yi
Y
Ding
Sheng-Song
SS
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D017313:Fenretinide / Q000737:chemistry; D005643:Fucose / Q000378:metabolism; D005647:Fucosyltransferases / Q000378:metabolism; D018093:Gelatinases / Q000037:antagonists & inhibitors; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C519080:N-retinoylproline; D018168:Receptors, Retinoic Acid; D017313:Fenretinide; D005643:Fucose; D014212:Tretinoin; D011392:Proline; D005647:Fucosyltransferases; D018093:Gelatinases