Document Detail


Reversal of mdr1-mediated multidrug resistance in human leukemia cells by a new spin-labeled derivative of podophyllotoxin.
MedLine Citation:
PMID:  20225656     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
GP7 (4-[4"-(2", 2", 6", 6"-tetramethyl-l"-piperidinyloxy) amino]-4'-demethyl epipodophyllotoxin) is a promising anticancer drug of the podophyllotoxin class. However, little is known about its anti-multidrug resistance effects. In the present study, we investigated the effects of GP7 on P-glycoprotein (P-gp) overexpression multidrug-resistant human leukemia K562/ADM cells with the comparison of VP-16 and K562 cells. GP7 inhibited the proliferation of K562/ADM cells in a concentration- or time-dependent manner, and the inhibitory effect of GP7 on K562/ADM cells was 1.50-fold higher than that of VP-16. GP7 caused G2/M phase accumulation but VP-16 caused S phase accumulation in K562/ADM and K562 cells. GP7 could induce apoptosis of both K562/ADM and K562 cell lines, but there was no significant difference between GP7- and VP-16-induced apoptotic ratios. GP7 could also induce typical apoptotic morphological changes and internucleosomal DNA fragmentation of K562/ADM and K562 cells, but DNA fragmentation induced by GP7 in K562/ADM cells was weaker than that in K562 cells. When treated with GP7 or VP-16 for 48 h, 128-256 microM GP7 induced more DNA fragmentation than VP-16 did, but 32-64 microM GP7 induced less DNA fragmentation than VP-16 did. GP7 could down-regulate the expression of P-gp in K562/ADM cells but VP-16 could not. Our findings suggest that GP7 may reverse multidrug resistance in human leukemia K562/ADM cells via down-regulation of P-gp expression.
Authors:
She-Ning Qi; Li-Juan Song; Yan Chen; Yuan-Xue Jing
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Die Pharmazie     Volume:  65     ISSN:  0031-7144     ISO Abbreviation:  Pharmazie     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-03-15     Completed Date:  2010-04-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9800766     Medline TA:  Pharmazie     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  117-21     Citation Subset:  IM    
Affiliation:
Department of Histology and Embryology, School of Basic Medicine, Lanzhou University, Lanzhou, P R China. qishening@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / administration & dosage,  therapeutic use*
Apoptosis / drug effects
Blotting, Western
Cell Division / drug effects
Cell Line, Tumor
DNA Fragmentation
DNA, Neoplasm / biosynthesis,  genetics
Down-Regulation
Drug Resistance, Neoplasm / genetics*
Electrophoresis, Agar Gel
Flow Cytometry
G2 Phase / drug effects
Humans
K562 Cells
Leukemia / drug therapy*,  pathology
P-Glycoprotein / antagonists & inhibitors*,  biosynthesis,  genetics
Podophyllotoxin / administration & dosage,  analogs & derivatives*,  therapeutic use*
Spin Labels
Tetrazolium Salts
Thiazoles
Chemical
Reg. No./Substance:
0/ABCB1 protein, human; 0/Antineoplastic Agents, Phytogenic; 0/DNA, Neoplasm; 0/P-Glycoprotein; 0/Spin Labels; 0/Tetrazolium Salts; 0/Thiazoles; 298-93-1/thiazolyl blue; 518-28-5/Podophyllotoxin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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