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.

• Authors: L W Fu, Q C Pan, W L Huang, X P Yang
• Journal: Zhongguo yao li xue bao = Acta pharmacologica Sinica (Zhongguo Yao Li Xue Bao) Vol. 19 Issue 1 Pg. 77-80 (Jan 1998) ISSN: 0253-9756 [Print] China
• PMID: 10375766 (Publication Type: Journal Article)

Chemical References

• Indoles
• Morpholines
• Doxorubicin
• HWL 12
• Fura-2

Topics

• Breast Neoplasms (metabolism, pathology)
• Doxorubicin (metabolism)
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Fura-2 (metabolism)
• Humans
• Indoles (pharmacology)
• Morpholines (pharmacology)
• Tumor Cells, Cultured (metabolism)