ABSTRACT
The inhibitory activities of Schiff bases of hydroxysemicarbazide (HSC) against eight human and murine tumor cell lines and one non-cancer cell line were studied using MTS/PES microculture tetrazolium and methylene blue assays. Compounds 1 (1-[9-(10-methylanthryl)methylene]-4-HSC), 2 (1-[2-hydroxy-3,5-dibromobenzylidene]-4-HSC) and 3 (1-[2,3,4-trihydroxybenzylidene]-4-HSC), which have been shown to be active against murine leukemia L1210 cells in our laboratories, inhibited human leukemia CCRF-CEM cells with similar IC50s ranging from 2.7 to 7.0 microM. Of the compounds tested against attached tumor cell lines (B16, CHO, HT29, ZR75) at 50 microM concentration, compound 1 showed the strongest inhibition, followed by 4 (1-[2-(5-nitrothienyl)methylene]-4-HSC), 2 and 5 (1-[2-hydroxy-3,5-diiodobenzylidene]-4-HSC) with more than 50% inhibition. The IC50s of compound 1 were found to range from 2.7 to 12 microM against the attached tumor cell lines examined. As compared with hydroxyurea, compound 1 had more favorable selectivity against tumor cells. Further more, compound 1 was found to have IC50s of 2.8 and 6.5 microM against hydroxyurea-resistant and gemcitabine-resistant KB cells, respectively, but had no cross-resistance with hydroxyurea and gemcitabine (two known ribonucleotide reductase inhibitors acting at different sites of the same enzyme). In conclusion, several Schiff bases of HSC showed inhibition of tumor cell growth at micromolar concentration and had no cross-resistance with hydroxyurea-resistant KB cells.
Subject(s)
Antineoplastic Agents/pharmacology , Schiff Bases/pharmacology , Semicarbazides/pharmacology , 3T3 Cells/drug effects , Animals , CHO Cells/drug effects , Cell Division/drug effects , Cricetinae , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Growth Inhibitors/pharmacology , Humans , Inhibitory Concentration 50 , Mice , Tumor Cells, Cultured/drug effectsABSTRACT
Sialyltransferase enzyme levels (Sialtx) CEA, and 10 standard laboratory tests were studied in 50 patients with treated, recurrent, or disseminated breast carcinoma. All groups of patients had elevated mean Sialtx activity (CPM/mg protein) as compared with normal controls. Sialtx levels (expressed as % of normal controls) of patients with disseminated lesions were significantly elevated as compared to patients without evidence of disease or with only soft tissue recurrences, whereas CEA and alkaline phosphatase levels were significantly elevated (peripheral blood lymphocyte count, total protein and albumin levels significantly decreased) in patients with recurrent disease of all sites. Among patients with disseminated breast cancer and normal CEA levels, about 50% had markedly elevated Sialtx activities. From our limited experience, it appears that Sialtx study is of value when CEA failed to indicate the presence of breast malignancy. Further testing including serial studies should be done to better define its clinical usefulness.
