Inhibition of CMP-sialic acid transport in human liver and colorectal cancer cell lines by a sialic acid nucleoside conjugate (KI-8110).
The sialic acid nucleoside conjugate KI-8110 has been shown to inhibit the formation of hepatic metastases from human colorectal cancer cell lines in a nude mouse intrasplenic injection model. The compound does not inhibit sialyltransferases from either human colorectal tumor cells or human liver. Transport of CMP-sialic acid into endoplasmic reticulum and Golgi vesicles is inhibited and can account for the reduction in surface sialic acid found on treated cell lines. Only a 50% inhibition of CMP-sialic acid transport could be achieved suggesting the presence of more than one transport protein with differing specificities.
Harvey
B E
BE
Laboratory of Cancer Biology, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02115.
Thomas
P
P
D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism*; D003568:Cytidine Monophosphate / Q000494:pharmacology; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid / Q000378:metabolism*; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D012799:Sialyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D006027:Glycosides; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; C047714:KI 8110; D012799:Sialyltransferases; D003568:Cytidine Monophosphate; D014529:Uridine; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase