title: In vitro activity of titanocenedichloride versus cisplatin in four ovarian carcinoma cell lines evaluated by a microtiter plate ATP bioluminescence assay.
abstract: Titanocenedichloride (MKT 4) is a novel anticancer drug with a broad spectrum of activity in mammalian tumors. We investigated the anticancer efficacy of MKT 4 versus cisplatin and its chemomodulation by buthionine sulfoximine (BSO) in four different human ovarian carcinoma (OvCA) cell lines derived from both primary (A2780. OTN 14) and recurrent tumors (SKOV-3 and OV-MZ-1b) using an in vitro microplate ATP bioluminescence assay (ATP-TCA). Sensitivity against cisplatin was higher in A2780 and OTN 14 compared with MKT 4, whereas the opposite was found in SKOV-3 and OV-MZ-1b cells. In A2780, SKOV-3 and OV-MZ-1b, the cytotoxicity of both agents could be effectively improved by BSO with supraadditive effects observed for MKT 4 in all three cell lines. In OTN 14, however, BSO treatment failed to increase the cytotoxicity of both cisplatin and MKT 4. These results suggest antineoplastic activity of MKT 4 in cisplatin-sensitive and mainly in cisplatin-resistant OvCA cells which can be significantly modulated by BSO-mediated glutathione depletion. Since antineoplastic activity of both cisplatin and MKT-4 observed in OTN 14 could not be reversed by BSO, other mechanisms of drug resistance different from the glutathione redox cycle are likely to be important for both metal compounds.
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital, Bonn, Germany.
authors.forename: C M
authors.initials: CM
authors.lastname: Kurbacher
authors.forename: H W
authors.initials: HW
authors.lastname: Bruckner
authors.forename: P E
authors.initials: PE
authors.lastname: Andreotti
authors.forename: J A
authors.initials: JA
authors.lastname: Kurbacher
authors.forename: G
authors.initials: G
authors.lastname: Sass
authors.forename: D
authors.initials: D
authors.lastname: Krebs
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000255:Adenosine Triphosphate / Q000032:analysis; D019328:Buthionine Sulfoximine; D002452:Cell Count / Q000379:methods*; D016923:Cell Death / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007928:Lethal Dose 50; D008163:Luminescent Measurements; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D009942:Organometallic Compounds; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D000255:Adenosine Triphosphate; C020528:titanocene dichloride; D002945:Cisplatin