Effect of galactose on interaction of N-(2-hydroxypropyl)methacrylamide copolymers with hepatoma cells in culture: Preliminary application to an anticancer agent, daunomycin
✍ Scribed by Kathryn B. O'Hare; Isabella C. Hume; Lynne Scarlett; Vladimir Chytrý; Pavla Kopećar;ková; Jindřich Kopeček; Ruth Duncan
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 824 KB
- Volume
- 10
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
A series of copolymers were prepared containing 1,2:3,4-di-O-isopropylidene-6-O-methacryloyl-cr-~galactopyranose (0 to 99 mol %), methacryoyltyrosinamide and N-(2-hydroxypropy1)methacrylamide (99 to 0 mol %). The effect of galactose content on interaction with hepatoma cells in vitro was studied. Increased galactose content caused increased accumulation of N-(2-hydroxypropy1)methacrylamide copolymers by two human hepatoma cell lines (Hep Gz and SAH), but accumulation by rat and mouse hepatoma (HTC and NCTC) was not galactose dependent. Accumulation of N-(2hydroxypropyl)methacrylamide copolymers by Hep Gz was shown to be an active process, being inhibited by low temperature and by the metabolic inhibitor 2,4dinitrophenol . Addition of Nacet y lgalactosamine and polymer-galactose to the incubation medium resulted in a concentration-dependent inhibition of accumulation of galactose-containing polymers. Addition of fucose or galactose was without effect at the concentrations used. Polymers bearing galactosamine or fucosylamine residues and, in addition, daunomycin were evaluated for cytotoxicity against Hep Gz and SAH. N-(2-Hydroxypropy1)methacrylamide copolymer-bound daunomydin produced a dose-dependent inhibition of DNA synthbsis (measured by incorporation of [3H]thymidine), and the galactose-containing polymer showed greatest inhibition.
Hepatocellular carcinoma is one of the most prevalent cancers in the world; recent evidence suggests that in some countries the incidence is rising (1). In addition, met.astases in the liver are often the cause of death in patients with tumors of colorectal, breast or other origin. Both primary and metastatic liver cancer are notoriously resistant to conventional chemotherapeutic agents. In recent years, considerable effort has been made to improve delivery of these drugs in an attempt to improve their therapeutic indices. Regional therapy by hepatic