Reversal of tumor multidrug resistance by 2-phenyl-3-(3',5'-dimorpholinomethyl-4'-hydroxy)-benzoyl-indole (HWL-12)
Abstract
AIM: To explore the reversal of multidrug resistance (MDR) by indole derivative HWL-12.
METHODS: Cytotoxicity was determined by tetrazolium (MTT) assay. The function of P-gp was examined by Fura 2-AM assay. Cellular accumulation of doxorubicin (Dox) was measured by fluorescence spectrophotometry.
RESULTS: HWL-12 10 mumol.L-1 markedly increased Fura-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 presence of HWL-12 on the MCF-7/ADR cells. No effect was observed for Dox accumulation in the presence of high Ca2+ (addition of CaCl2) or low Ca2+ (addition of egtazic acid).
CONCLUSION: HWL-12 has a potent MDR reversal action which was associated with the increase of cellular Dox accumulation in MDR cells and not related with calcium ion concentration.
Keywords:
METHODS: Cytotoxicity was determined by tetrazolium (MTT) assay. The function of P-gp was examined by Fura 2-AM assay. Cellular accumulation of doxorubicin (Dox) was measured by fluorescence spectrophotometry.
RESULTS: HWL-12 10 mumol.L-1 markedly increased Fura-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 presence of HWL-12 on the MCF-7/ADR cells. No effect was observed for Dox accumulation in the presence of high Ca2+ (addition of CaCl2) or low Ca2+ (addition of egtazic acid).
CONCLUSION: HWL-12 has a potent MDR reversal action which was associated with the increase of cellular Dox accumulation in MDR cells and not related with calcium ion concentration.