PMID: 19947169Dec 2, 2009Paper

Reversal of P-glycoprotein-mediated multidrug resistance by guggulsterone in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells

Die Pharmazie
Hong-Bin XuGuo-Qing Liu

Abstract

Multidrug resistance (MDR) has been a major problem in cancer chemotherapy. The development of P-glycoprotein inhibitors could be effective to reverse multidrug resistance. The aim of this study was to observe the effects of guggulsterone, the active component of gugulipid, on multidrug resistance in doxorubicin-resistant K562 cells (K562/DOX) and the parental K562 cells. Its cytotoxicity and reversal effects on multidrug resistance were assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Apoptosis percentage of cells was obtained from Annexin V/fluorescein isothiocyanate (FITC) and propridium iodide (PI) double staining. The effects of guggulsterone on P-glycoprotein activity were evaluated by measuring rhodamine 123 (Rh123)-associated mean fluorescence intensity and P-glycoprotein expression on the basis of the flow cytometric technology, respectively. The results showed that guggulsterone up to 100 microM had little cytotoxicity against K562/DOX cells. When combined with doxorubicin, it significantly promoted the sensitivity of K562/DOX cells toward doxorubicin through increasing intracellular accumulation of doxorubicin in a dose-dependent manner. Further study demonstrated that the inhibit...Continue Reading

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.