title: Reversal of tumor multidrug resistance by 2-phenyl-3-(3',5'-dimorpholinomethyl-4'-hydroxy)-benzoyl-indole (HWL-12).
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cancer Institute, Sun Yat-Sen University of Medical Sciences, Guangzhou, China.
authors.forename: L W
authors.initials: LW
authors.lastname: Fu
authors.forename: Q C
authors.initials: QC
authors.lastname: Pan
authors.forename: W L
authors.initials: WL
authors.lastname: Huang
authors.forename: X P
authors.initials: XP
authors.lastname: Yang
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D016257:Fura-2 / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D007211:Indoles; D009025:Morpholines; D004317:Doxorubicin; C120237:HWL 12; D016257:Fura-2