Exploiting the metabolic energy demands of drug efflux pumps provides a strategy to overcome multidrug resistance in cancer

2021 ◽  
Vol 1865 (8) ◽  
pp. 129915
Author(s):  
Xuexin Gao ◽  
Doriane Aguanno ◽  
Mary Board ◽  
Richard Callaghan
2020 ◽  
Author(s):  
Yaojun Tong ◽  
Nuo Sun ◽  
Xiangming Wang ◽  
Qi Wei ◽  
Yu Zhang ◽  
...  

AbstractClinical use of antimicrobials faces great challenges from the emergence of multidrug resistant (MDR) pathogens. The overexpression of drug efflux pumps is one of the major contributors to MDR. It is considered as a promising approach to overcome MDR by reversing the function of drug efflux pumps. In the life-threatening fungal pathogen Candida albicans, the major facilitator superfamily (MFS) transporter Mdr1p can excrete many structurally unrelated antifungals, leading to multidrug resistance. Here we report a counterintuitive case of reversing multidrug resistance in C. albicans by using a natural product berberine to hijack the overexpressed Mdr1p for its own importation. Moreover, we illustrate that the imported berberine accumulates in mitochondria, and compromises the mitochondrial function by impairing mitochondrial membrane potential and mitochondrial Complex I. It results in the selective elimination of Mdr1p overexpressed C. albicans cells. Furthermore, we show that berberine treatment can prolong the mean survival time (MST) of mice with a blood-borne dissemination of Mdr1p overexpressed multidrug resistant candidiasis. This study provided a potential direction of novel anti-MDR drug discovery by screening for multidrug efflux pump converters.


Planta Medica ◽  
2016 ◽  
Vol 82 (13) ◽  
pp. 1180-1185 ◽  
Author(s):  
Shweta Nim ◽  
Andreia Mónico ◽  
Manpreet Rawal ◽  
Noélia Duarte ◽  
Rajendra Prasad ◽  
...  

2008 ◽  
Vol 28 (4) ◽  
pp. 217-228 ◽  
Author(s):  
Sneh Lata Panwar ◽  
Ritu Pasrija ◽  
Rajendra Prasad

The development of MDR (multidrug resistance) in yeast is due to a number of mechanisms. The most documented mechanism is enhanced extrusion of drugs mediated by efflux pump proteins belonging to either the ABC (ATP-binding cassette) superfamily or MFS (major facilitator superfamily). These drug-efflux pump proteins are localized on the plasma membrane, and the milieu therein affects their proper functioning. Several recent studies demonstrate that fluctuations in membrane lipid composition affect the localization and proper functioning of the MDR efflux pump proteins. Interestingly, the efflux pumps of the ABC superfamily are particularly susceptible to imbalances in membrane-raft lipid constituents. This review focuses on the importance of the membrane environment in functioning of the drug-efflux pumps and explores a correlation between MDR and membrane lipid homoeostasis.


Author(s):  
Wouter B. Nagengast ◽  
Thijs H. Oude Munnink ◽  
Eli C. F. Dijkers ◽  
Geke A. P. Hospers ◽  
Adrienne H. Brouwers ◽  
...  

2020 ◽  
Vol 27 (33) ◽  
pp. 5510-5529
Author(s):  
Zengtao Wang ◽  
Qingqing Meng ◽  
Shaoshun Li

Background: Multidrug Resistance (MDR) is defined as a cross-resistance of cancer cells to various chemotherapeutics and has been demonstrated to correlate with drug efflux pumps. Visualization of drug efflux pumps is useful to pre-select patients who may be insensitive to chemotherapy, thus preventing patients from unnecessary treatment. Near-Infrared (NIR) imaging is an attractive approach to monitoring MDR due to its low tissue autofluorescence and deep tissue penetration. Molecular NIR imaging of MDR cancers requires stable probes targeting biomarkers with high specificity and affinity. Objective: This article aims to provide a concise review of novel NIR probes and their applications in MDR cancer treatment. Results: Recently, extensive research has been performed to develop novel NIR probes and several strategies display great promise. These strategies include chemical conjugation between NIR dyes and ligands targeting MDR-associated biomarkers, native NIR dyes with inherent targeting ability, activatable NIR probes as well as NIR dyes loaded nanoparticles. Moreover, NIR probes have been widely employed for photothermal and photodynamic therapy in cancer treatment, which combine with other modalities to overcome MDR. With the rapid advancing of nanotechnology, various nanoparticles are incorporated with NIR dyes to provide multifunctional platforms for controlled drug delivery and combined therapy to combat MDR. The construction of these probes for MDR cancers targeted NIR imaging and phototherapy will be discussed. Multimodal nanoscale platform which integrates MDR monitoring and combined therapy will also be encompassed. Conclusion: We believe these NIR probes project a promising approach for diagnosis and therapy of MDR cancers, thus holding great potential to reach clinical settings in cancer treatment.


2014 ◽  
Vol 21 ◽  
pp. 92
Author(s):  
K. Ganguly ◽  
J.L. Phillips ◽  
M.S. Wren ◽  
P.E. Pardington ◽  
S. Gnanakaran ◽  
...  

2004 ◽  
Vol 40 (14) ◽  
pp. 2064-2070 ◽  
Author(s):  
J. Bart ◽  
H. Hollema ◽  
H.J.M. Groen ◽  
E.G.E. de Vries ◽  
N.H. Hendrikse ◽  
...  

Author(s):  
Viola Camilla Scoffone ◽  
Tom Coenye ◽  
Giovanna Riccardi ◽  
Silvia Buroni

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