Thioltransferase overexpression increases resistance of MCF-7 cells to adriamycin

Thioltransferase, a small redox protein with thiol-disulfide oxidoreductase and dehydroascorbate reductase activities, has been reported to be express ed at higher levels in Adriamycin-resistant MCF-7 human breast tumor cells (MCF-7 ADR(R)) when compared with Adriamycin sensitive MCF-7 WT (MCF-7 WT) cells. The present study examined the effects of stably transfecting MCF-7 WT cells with the cDNA for human thioltransferase and the effects of subseq uent Adriamycin cytotoxicity in the MCF-7 WT transfected cells. All transfe cted cell lines overexpressing thioltransferase activity were more resistan t to Adriamycin than untransfected MCF-7 WT cells, supporting the hypothesi s that increases in thioltransferase expression are related to Adriamycin r esistance. This resistance was independent of the ability of thioltransfera se to catalyze reduction of dehydroascorbic acid to ascorbic acid, as the a ddition of an ascorbate generating derivative, L-ascorbic acid-2-phosphate, to the media did not additionally increase Adriamycin resistance. (C) 1999 Elsevier Science Inc.