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Inhibition of P-glycoprotein activity and reversal of cancer multidrug resistance by Momordica charantia extract.

Abstract：

PURPOSE:Multidrug resistance (MDR) is known as a problem limiting the success of therapy in patients treated long term with chemotherapeutic drugs. The drug resistance is mainly due to the overexpression of the 170 kDa P-glycoprotein (Pgp), which causes a reduction in drug accumulation in the cancer cells. In this study, novel chemical modulator(s) from bitter melon (Momordica charantia L.) extracts obtained from leaves, fruits and tendrils were tested for their abilities to modulate the function of Pgp and the MDR phenotype in the multidrug-resistant human cervical carcinoma KB-V1 cells (high Pgp expression) in comparison with wildtype drug-sensitive KB-3-1 cells (lacking Pgp). METHODS:The KB-V1 and KB-3-1 cells were exposed to bitter melon extracts in the presence of various concentrations of vinblastine, and cytotoxicity was assessed by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Relative resistance was calculated as the ratio of the IC50 value of the KB-V1 cells to the IC50 value of the KB-3-1 cells. Accumulation and efflux of vinblastine in KB-V1 and KB-3-1 cells were measured using a [3H]-vinblastine incorporation assay. RESULTS:The leaf extracts increased the intracellular accumulation of [3H]-vinblastine in KB-V1 cells in a dose-dependent manner, but extracts from the fruits and tendrils had no effect. By modulating Pgp-mediated vinblastine efflux, the leaf extracts decreased the [3H]-vinblastine efflux in KB-V1 cells in a dose-dependent manner, but not in KB-3-1 cells. Treatment of drug-resistant KB-V1 cells with bitter melon leaf extracts increased their sensitivity to vinblastine, but similar treatment of KB-3-1 cells showed no modulating effect. The fruit and tendril extracts did not affect the MDR phenotype in either cell line. CONCLUSION:The leaf extracts from bitter melon were able to reverse the MDR phenotype, which is consistent with an increase in intracellular accumulation of the drug. The exact nature of the active components of bitter melon leaf extracts remains to be identified.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Limtrakul P,Khantamat O,Pintha K

doi

10.1007/s00280-004-0848-4

keywords:

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

525-30

issue

6

eissn

0344-5704

issn

1432-0843

journal_volume

54

pub_type

杂志文章

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