Inhibition of CMP-sialic acid transport in human liver and colorectal cancer cell lines by a sialic acid nucleoside conjugate (KI-8110)

Abstract

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.