dihydropyridines and Carcinoma--Hepatocellular

Three groups of synthetic lipids are chosen for studies: (1) 1,4-dihydropyridines (1,4-DHPs) containing two cationic moieties and their analogues; (2) 3,4-dihydro-2(1

Topics: Animals; Carcinoma, Hepatocellular; Cell Proliferation; Dihydropyridines; Fibrosarcoma; Humans; Liver Neoplasms; Lung Diseases; Mice; Molecular Structure; NIH 3T3 Cells; Pyridones; Tumor Cells, Cultured; Vinyl Compounds

A novel method for preparation of a new class of dihydropyridine thioglycosides and their corresponding dehydrogenated forms, via reaction of piperidinium salts of dihydropyridinethiones with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galactopyranosyl bromides has been studied. The evaluation of antiproliferative activity against HepG-2 cell lines (liver carcinoma cell lines) of the dihydropyridine thioglycosides and pyridine thioglycosides revealed that many of the thioglycosides have interesting antitumor activities specifically 5c, 5g, 5l, 5o, 5p, 7a, 7i, 7p, 8b, 8f, 8s, and 8v.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Proliferation; Cell Survival; Dihydropyridines; Drug Design; Hep G2 Cells; Humans; Liver Neoplasms; Molecular Structure; Oxidation-Reduction; Structure-Activity Relationship; Thioglycosides

Virally-induced hepatocellular carcinomas (HCC) are intrinsically resistant to cancer chemotherapy partly due to increased expression of p-glycoprotein (pgp). In this study, we determined that pgp expressed in woodchuck HCC had binding properties were similar to the drug resistant human pgp. Pgp drug binding properties were characterized by photoaffinity labeling with the calcium channel blocker [3H]azidopine (AZD). AZD bound pgp in HCC but not in non-tumor liver samples, and binding was confirmed by competition with Adriamycin (IC50 = 10 microM) and actinomycin D (IC50 = 1 microM). In summary, WHV-induced HCC overexpress a pgp which binds anticancer drugs suggesting a common pathway for drug resistance.

Topics: Affinity Labels; Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Azides; Binding, Competitive; Carcinoma, Hepatocellular; Dihydropyridines; Doxorubicin; Liver Neoplasms; Marmota