Multidrug Efflux Pumps and Cancer Stem Cells: Insights Into Multidrug Resistance and Therapeutic Development

2011 ◽  
Vol 89 (4) ◽  
pp. 491-502 ◽  
Author(s):  
K Moitra ◽  
H Lou ◽  
M Dean
2003 ◽  
Vol 47 (8) ◽  
pp. 2413-2417 ◽  
Author(s):  
Nazmul Huda ◽  
Eun-Woo Lee ◽  
Jing Chen ◽  
Yuji Morita ◽  
Teruo Kuroda ◽  
...  

ABSTRACT A gene responsible for multidrug resistance was cloned from the chromosomal DNA of non-O1 Vibrio cholerae NCTC 4716 by using as a host drug-hypersensitive Escherichia coli strain KAM32, which lacks major multidrug efflux pumps. E. coli cells transformed with the gene showed elevated levels of resistance to a number of structurally dissimilar drugs, such as tetracycline, norfloxacin, ciprofloxacin, doxorubicin, daunomycin, 4′,6-diamidino-2-phenylindole, and Hoechst 33342. We determined the nucleotide sequence and found one open reading frame. We designated the gene vcaM. The deduced product, VcaM, seems to be a polypeptide with 619 amino acid residues (69 kDa) that has a putative topology of six transmembrane segments in the N-terminal hydrophobic domain, followed by an ATP binding domain in the C-terminal hydrophilic region. The sequence of VcaM was shown to be similar to those of human multidrug resistance proteins P-glycoprotein MDR1 and lactococcal LmrA, which are driven by ATP. The efflux of Hoechst 33342 and doxorubicin from cells possessing VcaM was detected. The efflux activity was inhibited by reserpine and sodium o-vanadate, which are potent inhibitors of MDR1 and LmrA. Thus, we conclude that VcaM is a member of the family of multidrug efflux pumps of the ATP binding cassette type and the first experimentally proven example of a multidrug efflux pump of this family in gram-negative bacteria.


2012 ◽  
Vol 8 ◽  
pp. 1700-1704 ◽  
Author(s):  
Torsten Dittrich ◽  
Nils Hanekop ◽  
Nacera Infed ◽  
Lutz Schmitt ◽  
Manfred Braun

The inhibition of ABC (ATP binding cassette) transporters is considered a powerful tool to reverse multidrug resistance. Zosuquidar featuring a difluorocyclopropyl-annulated dibenzosuberyl moiety has been found to be an inhibitor of the P-glycoprotein, one of the best-studied multidrug efflux pumps. Twelve 5-oxyisoquinoline derivatives, which are analogues of zosuquidar wherein the dibenzosuberyl-piperazine moiety is replaced by either a diarylaminopiperidine or a piperidone-derived acetal or thioacetal group, have been synthesized as pure enantiomers. Their inhibitory power has been evaluated for the bacterial multidrug-resistance ABC transporter LmrCD and fungal Pdr5. Four of the newly synthesized compounds reduced the transport activity to a higher degree than zosuquidar, being up to fourfold more efficient than the lead compound in the case of LmrCD and about two times better for Pdr5.


Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
R Pereda-Miranda ◽  
L Chérigo ◽  
M Fragoso-Serrano ◽  
N Jacobo-Herrera ◽  
GW Kaatz ◽  
...  

2016 ◽  
Vol 16 (3) ◽  
pp. 172-177 ◽  
Author(s):  
Aslan Bijari ◽  
Leila Azimi ◽  
Fatemeh Fallah ◽  
Abdollah Ardebili ◽  
Elnaz Lari ◽  
...  

2021 ◽  
Vol 54 (4) ◽  
pp. 930-939
Author(s):  
Helen I. Zgurskaya ◽  
John K. Walker ◽  
Jerry M. Parks ◽  
Valentin V. Rybenkov

2021 ◽  
Author(s):  
Peter J. F. Henderson ◽  
Claire Maher ◽  
Liam D. H. Elbourne ◽  
Bart A. Eijkelkamp ◽  
Ian T. Paulsen ◽  
...  

2005 ◽  
Vol 49 (11) ◽  
pp. 999-1002 ◽  
Author(s):  
Takehiko Mima ◽  
Hiroshi Sekiya ◽  
Tohru Mizushima ◽  
Teruo Kuroda ◽  
Tomofusa Tsuchiya

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