title: Antitumour activity of suramin analogues in human tumour cell lines and primary cultures of tumour cells from patients.
abstract: Suramin has shown promising antitumour activity against several tumour types, both in vitro and in vivo, but the clinical utility of this compound is hampered by its unfavourable toxicity profile. In the present study, the semi-automated fluorometric microculture cytotoxicity assay (FMCA) was employed for evaluation of the cytotoxicity of seven suramin analogues in vitro in a panel of human tumour cell lines and in primary cultures of tumour cells from patients. Like suramin, the analogues showed little sensitivity to resistance mechanisms involving P-glycoprotein, topoisomerase II, multidrug resistance associated protein and glutathione-mediated drug resistance. In the cell line panel, NF067 and FCE 26644 showed activity comparable with suramin. All analogues were less potent than suramin in patient cells except for FCE 26644. Correlation to suramin activity patterns in the cell line panel was highest for NF037 and low to moderate for the remaining analogues. In patient cells, high correlation coefficients were obtained for FCE 26644, NF110, NF031 and NF037. The results indicate that the cytotoxic activity of suramin on patient tumour cells is shared by the analogues with FCE 26644 being the most active. The pharmacophore for cytotoxicity in patient cells may be different from that observed in the cell lines.
authors.affiliation: Division of Clinical Pharmacology, University Hospital, Uppsala University, S-751 85, Uppsala, Sweden. sumeer.dhar@klinfarm.uu.se
authors.forename: S
authors.initials: S
authors.lastname: Dhar
authors.forename: J
authors.initials: J
authors.lastname: Gullbo
authors.forename: K
authors.initials: K
authors.lastname: Csoka
authors.forename: E
authors.initials: E
authors.lastname: Eriksson
authors.forename: K
authors.initials: K
authors.lastname: Nilsson
authors.forename: P
authors.initials: P
authors.lastname: Nickel
authors.forename: R
authors.initials: R
authors.lastname: Larsson
authors.forename: P
authors.initials: P
authors.lastname: Nygren
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D005470:Fluorometry; D006801:Humans; D013498:Suramin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D013498:Suramin