Document Detail

Reversal of P-glycoprotein-mediated multidrug resistance by guggulsterone in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells.
MedLine Citation:
PMID:  19947169     Owner:  NLM     Status:  MEDLINE    
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 inhibitory effect of guggulsterone on P-glycoprotein activity was the major cause of increased stagnation of doxorubicin inside K562/DOX cells, indicating that guggulsterone may effectively reverse multidrug resistance in K562/DOX cells via inhibiting expression and drug-transport function of P-glycoprotein.
Hong-Bin Xu; Ling Li; Guo-Qing Liu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Die Pharmazie     Volume:  64     ISSN:  0031-7144     ISO Abbreviation:  Pharmazie     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-12-01     Completed Date:  2010-01-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9800766     Medline TA:  Pharmazie     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  660-5     Citation Subset:  IM    
Department of Pharmacy, Tenth People's Hospital, Tongji University, Shanghai, China.
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MeSH Terms
Antibiotics, Antineoplastic / metabolism,  pharmacology*
Apoptosis / drug effects
Calcium Channel Blockers / pharmacology
Cell Line, Tumor
Cell Survival / drug effects
Doxorubicin / metabolism,  pharmacology*
Drug Resistance, Multiple / drug effects*
Drug Resistance, Neoplasm / drug effects*
Flow Cytometry
Fluorescent Dyes
K562 Cells
Leukemia, Myeloid / drug therapy*,  pathology
P-Glycoproteins / antagonists & inhibitors*,  chemistry*,  metabolism
Pregnenediones / pharmacology*
Rhodamine 123
Verapamil / pharmacology
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Calcium Channel Blockers; 0/Fluorescent Dyes; 0/P-Glycoproteins; 0/Pregnenediones; 23214-92-8/Doxorubicin; 52-53-9/Verapamil; 62669-70-9/Rhodamine 123; 95975-55-6/pregna-4,17-diene-3,16-dione

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