REVERSAL OF TUMOR MULTIDRUG-RESISTANCE BY ',5'-DIMORPHOLINOMETHYL-4'-HYDROXY)-BENZOYL-INDOLE (HWL-12)

AIM: To explore the reversal of multidrug resistance (MDR) by indole d erivative HWL-12. METHODS: Cytotoxicity was determined by tetrazolium (MTT) assay. The function of P-gp was examined by Fura 2-AM assay. Cel lular accumulation of doxorubicin (Dox) was measured by fluorescence s pectrophotometry. RESULTS: HWL-12 10 mu mol.L-1 markedly increased Fur a-2 accumulation and was 17.2-fold reversal of MDR in MCF-7/ADR cells. The cellular Dox accumulation in MDR cells was increased in the prese nce of HWL-12 on the MCF-7/ADR cells. No effect was observed for Dox a ccumulation in the presence of high Ca2+ (addition of CaCl2) or low Ca 2+ (addition of egtazic acid). CONCLUSION: HWL-12 has a potent MDR rev ersal action which was associated with the increase of cellular Dox ac cumulation in MDR cells and not related with calcium ion concentration .