Multidrug resistance proteins (MRPs): Structure, function and the overcoming of cancer multidrug resistance

Wang, Jingquan; Yang, Yuqi; Cai, Chao-Yun; Teng, Quincy; Cui, Qingbin; Lin, Jun; Assaraf, Yehuda G.; Chen, Zhe‐Sheng

doi:10.1016/j.drup.2021.100743

Cited by 118 publications

(71 citation statements)

References 213 publications

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“…In the past decade, knowledge of weak points of MDR mechanisms enabled scientists to develop new strategies against MDR cancer cells. In addition to the above-mentioned MDR modulators, a lot of novel potential anticancer agents have been designed to overcome these mechanisms [65,66].…”

Section: Modulators Of Natural Originmentioning

confidence: 99%

Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy

et al. 2021

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Modifications of the composition or organization of the cancer cell membrane seem to be a promising targeted therapy. This approach can significantly enhance drug uptake or intensify the response of cancer cells to chemotherapeutics. There are several methods enabling lipid bilayer modifications, e.g., pharmacological, physical, and mechanical. It is crucial to keep in mind the significance of drug resistance phenomenon, ion channel and specific receptor impact, and lipid bilayer organization in planning the cell membrane-targeted treatment. In this review, strategies based on cell membrane modulation or reorganization are presented as an alternative tool for future therapeutic protocols.

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Section: Modulators Of Natural Originmentioning

confidence: 99%

Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy

et al. 2021

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“…ATP-binding cassette (ABC) transport proteins are ubiquitously present in the human body [1] , [2] , [3] , [4] , and hence, promote solute and drug distribution, influencing their pharmacokinetic. However, dysfunction of these efflux pumps contribute also to major human diseases.…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, only a small fraction of the 49 existing ABC transporters can be considered as well-studied, in particular ABCB1 [8] , [14] , [15] , [16] , [17] , [18] , [19] , ABCB11 [20] , [21] , [22] , ABCC1 [1] , [4] , [14] , [15] , [17] , [23] , [24] , and ABCG2 [14] , [15] , [17] , [25] . Less-studied ABC transporters that have found much less attention are ABCC2, ABCC4–5, and ABCC10 [1] , [4] , [14] , [24] , [26] , as well as – to a lesser extend – ABCA1 [27] , [28] , [29] , [30] , ABCB4 [14] , ABCC3 [1] , [4] , [14] , [24] , as well as ABCC7–9 and ABCC11 [1] , [4] , [31] , [32] . The remaining 34 transporters can be considered as under-studied which cannot be addressed by small-molecule modulators besides very rare exceptions.…”

Section: Introductionmentioning

confidence: 99%

“…As a logical consequence, the number of synthetic approaches to gain novel lead structures and potent modulators of ABC transporters is also very unequally distributed amongst the ABC transport proteins, and very scarce for under-studied ABC transporters. While many hundreds of small-molecule modulators of ABCB1 [14] , [15] , [16] , [17] , [18] , [19] , ABCC1 [1] , [4] , [14] , [15] , [17] , [23] , [24] , and ABCG2 [14] , [15] , [17] , [25] exist, synthetic approaches to target other ABC transporters have barely been reported. Rare exceptions are, for example, ABCC4 [33] , [34] , ABCC8 [35] , or ABCC10 [36] .…”

Section: Introductionmentioning

confidence: 99%

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Scaffold fragmentation and substructure hopping reveal potential, robustness, and limits of computer-aided pattern analysis (C@PA)

Namasivayam

Silbermann

Pahnke

et al. 2021

Computational and Structural Biotechnology Journal

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“…Later on, other efflux transporters, such as multidrug resistance protein 1 (MRP1, ABCC1 ) and breast cancer resistant protein (BCRP, ABCG2 ), also known as mitoxantrone resistant protein (MXR), were also associated with clinical MDR. Despite the extensive research with efflux transporter inhibitors, their success in clinical use has been modest, mainly because of the challenge of targeting these inhibitors only into the cancer cells [ 2 , 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Ganciclovir and Its Hemocompatible More Lipophilic Derivative Can Enhance the Apoptotic Effects of Methotrexate by Inhibiting Breast Cancer Resistance Protein (BCRP)

Markowicz-Piasecka

Huttunen

Montaser

et al. 2021

IJMS

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Efflux transporters, namely ATP-binding cassette (ABC), are one of the primary reasons for cancer chemoresistance and the clinical failure of chemotherapy. Ganciclovir (GCV) is an antiviral agent used in herpes simplex virus thymidine kinase (HSV-TK) gene therapy. In this therapy, HSV-TK gene is delivered together with GCV into cancer cells to activate the phosphorylation process of GCV to active GCV-triphosphate, a DNA polymerase inhibitor. However, GCV interacts with efflux transporters that are responsible for the resistance of HSV-TK/GCV therapy. In the present study, it was explored whether GCV and its more lipophilic derivative (1) could inhibit effluxing of another chemotherapeutic, methotrexate (MTX), out of the human breast cancer cells. Firstly, it was found that the combination of GCV and MTX was more hemocompatible than the corresponding combination with compound 1. Secondly, both GCV and compound 1 enhanced the cellular accumulation of MTX in MCF-7 cells, the MTX exposure being 13–21 times greater compared to the MTX uptake alone. Subsequently, this also reduced the number of viable cells (41–56%) and increased the number of late apoptotic cells (46–55%). Moreover, both GCV and compound 1 were found to interact with breast cancer resistant protein (BCRP) more effectively than multidrug-resistant proteins (MRPs) in these cells. Since the expression of BCRP was higher in MCF-7 cells than in MDA-MB-231 cells, and the cellular uptake of GCV and compound 1 was smaller but increased in the presence of BCRP-selective inhibitor (Fumitremorgin C) in MCF-7 cells, we concluded that the improved apoptotic effects of higher MTX exposure were raised mainly from the inhibition of BCRP-mediated efflux of MTX. However, the effects of GCV and its derivatives on MTX metabolism and the quantitative expression of MTX metabolizing enzymes in various cancer cells need to be studied more thoroughly in the future.

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Multidrug resistance proteins (MRPs): Structure, function and the overcoming of cancer multidrug resistance

Cited by 118 publications

References 213 publications

Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy

Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy

Scaffold fragmentation and substructure hopping reveal potential, robustness, and limits of computer-aided pattern analysis (C@PA)

Ganciclovir and Its Hemocompatible More Lipophilic Derivative Can Enhance the Apoptotic Effects of Methotrexate by Inhibiting Breast Cancer Resistance Protein (BCRP)

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