Effects of thaliblastine on cytotoxicity and DNA damage in drug-sensitive and -resistant rat ovarian tumor cells treated with cisplatin.

Abstract

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.

• Authors: G Chen, W J Zeller
• Journal: Anticancer research (Anticancer Res) 1993 Jan-Feb Vol. 13 Issue 1 Pg. 219-23 ISSN: 0250-7005 [Print] Greece
• PMID: 8476216 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Aporphines
• Benzylisoquinolines
• DNA, Neoplasm
• Isoquinolines
• thalicarpine
• Cisplatin

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacology)
• Aporphines (administration & dosage, pharmacology)
• Benzylisoquinolines
• Cisplatin (administration & dosage, pharmacology)
• DNA Damage (drug effects)
• DNA, Neoplasm (drug effects)
• Drug Interactions
• Drug Resistance
• Drug Screening Assays, Antitumor
• Female
• Isoquinolines (administration & dosage, pharmacology)
• Ovarian Neoplasms (drug therapy)
• Rats
• Tumor Cells, Cultured (drug effects)