Modulation of cisplatin cytotoxicity by sulphasalazine

摘要: The efficacy of cisplatin [cis-diamminedichloroplatinum (II); DDP] is hampered by acquired or de novo resistance malignant cells to its cytotoxic effects. We have previously reported that parallels glutathione S-transferase (GST) activity in several human small-cell lung cancer cell lines. In the presently described studies, we used sulphasalazine, an inhibitor GSTs, evaluate relative role GSTs mediating two lines, NCI H-69 and H-2496. line, which contained relatively higher GST than H-2496 line (317 +/- 7 vs 9 1 mU mg-1 protein respectively), also displayed a greater degree (IC50 values 25.0 3.9 4.5 1.0 microM respectively). Western blot Northern analyses purified revealed expression only pi-class both Sulphasalazine inhibited 10 for 12 H-2496) from lines competitive manner with similar Ki (6.5 7.9 Cytotoxicity studies sulphasalazine increased cytotoxicity towards Isobologram analysis showed synergistically enhanced magnitude synergy being remarkably cells. Our indicate clinically achievable concentrations may be useful modulating malignancies GST-pi content.