Reversal of tumor multidrug resistance by 2-phenyl-3-(3',5'-dimorpholinomethyl-4'-hydroxy)-benzoyl-indole (HWL-12).
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.
Fu
L W
LW
Cancer Institute, Sun Yat-Sen University of Medical Sciences, Guangzhou, China.
Pan
Q C
QC
Huang
W L
WL
Yang
X P
XP
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
D007211:Indoles; D009025:Morpholines; D004317:Doxorubicin; C120237:HWL 12; D016257:Fura-2