Effects of thaliblastine on cytotoxicity and DNA damage in drug-sensitive and -resistant rat ovarian tumor cells treated with cisplatin. Anticancer Res 1993;13(1):219-23
Date
01/01/1993Pubmed ID
8476216Scopus ID
2-s2.0-0027413154 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
Combination effects of cisplatin (DDP) and thaliblastine (TBL) in DDP-sensitive (0-342) and -resistant (0-342/DDP) rat ovarian tumor cells were investigated. TBL alone, at either 40 or 80 micrograms/ml, exerted higher cytotoxicity in the DDP-resistant 0-342/DDP cells than in the parental sensitive 0-342 cells in growth inhibition assay (% inhibitions: 12.5 and 42.8 in 0-342 cells vs. 37.5 and 66.1 in 0-342/DDP cells, at 40 and 80 micrograms/ml of TBL, respectively). TBL at 40 micrograms/ml showed an additive effect with DDP in the sensitive cells, while a synergistic cytotoxicity was observed in the resistant subline when the two drugs were used in combination, as exhibited by either % inhibition or cell viability. At 80 micrograms/ml of TBL, however, the combination effects were less than additive (infraadditive) in both lines, but still this treatment was more cytotoxic in 0-342/DDP cells. Alkaline elution assay showed that DDP induced higher DNA interstrand crosslings (ISCL) in 0-342 cells, while TBL produced DNA single strand breaks (SSB) in a dose-dependent manner in the resistant line but not in the sensitive cells. Combination of these two compounds resulted in a dramatic increase of DNA-SSB in 0-342/DDP cells. It is tentatively concluded that TBL might have some potential in combination with DDP to conquer the resistance in clinical use, which may result from its selective SSB-inducing activity in the resistant cells.
Author List
Chen G, Zeller WJAuthor
Guan Chen MD, PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents, Phytogenic
Aporphines
Benzylisoquinolines
Cisplatin
DNA Damage
DNA, Neoplasm
Drug Interactions
Drug Resistance
Drug Screening Assays, Antitumor
Female
Isoquinolines
Ovarian Neoplasms
Rats
Tumor Cells, Cultured