Evidence for Functional Discrimination Between Leukemic Cells Overexpressing Multidrug-Resistance Associated Protein and P-Glycoprotein

Benderra, Zineb; Morjani, Hamid; Trussardi, Aurélie; Manfait, Michel

doi:10.1007/978-1-4615-4811-9_17

Cited by 7 publications

(4 citation statements)

References 20 publications

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“…Another impediment to treatment, which is present in MDR cells, involves the sequestration of drugs within cytoplasmic vesicles, followed by drug extrusion out of the cell [155]. Drug sequestration in MDR cells is achieved through the maintenance of abnormally elevated pH gradients across organelle membranes -by the activity of H + -ATPase, an ATP-dependent pump [156,157]. The combination of several mechanisms of drug resistance complicates chemotherapy and reinforces the need for developing novel drug formulations effective against drug resistant cancers.…”

Section: Phenotype-selective Sensitization Of Mdr Tumors By Pluronic ®mentioning

confidence: 99%

Polymer genomics: An insight into pharmacology and toxicology of nanomedicines☆

Kabanov

2006

Advanced Drug Delivery Reviews

189

122

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Synthetic polymers and nanomaterials display selective phenotypic effects in cells and in the body signal transduction mechanisms involved in inflammation, differentiation, proliferation, and apoptosis. When physically mixed or covalently conjugated with cytotoxic agents, bacterial DNA or antigens, polymers can drastically alter specific genetically controlled responses to these agents. These effects, in part, result from cooperative interactions of polymers and nanomaterials with plasma cell membranes and trafficking of polymers and nanomaterials to intracellular organelles. Cells and whole organism responses to these materials can be phenotype or genotype dependent. In selected cases, polymer agents can bypass limitations to biological responses imposed by the genotype, for example, phenotypic correction of immune response by polyelectrolytes. Overall, these effects are relatively benign as they do not result in cytotoxicity or major toxicities in the body. Collectively, however, these studies support the need for assessing pharmacogenomic effects of polymer materials to maximize clinical outcomes and understand the pharmacological and toxicological effects of polymer formulations of biological agents, i.e. polymer genomics.

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Section: Phenotype-selective Sensitization Of Mdr Tumors By Pluronic ®mentioning

confidence: 99%

Polymer genomics: An insight into pharmacology and toxicology of nanomedicines☆

Kabanov

2006

Advanced Drug Delivery Reviews

189

122

View full text Add to dashboard Cite

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“…In addition, it has to be emphasized also that overexpression of Pgp is not the only factor implicated in the appearance of the MDR phenotype. The MDR cells frequently express other efflux proteins, such as MRP [5,6], have high levels of H + -ATPase [8] and exhibit activated GSH/GST detoxification system [7]. These and possibly some other factors could impose high energy requirements in MDR cells and collectively contribute to the elevated responsiveness of these cells to Pluronic.…”

Section: Correlation Between Atp Depletion and Pgp Expressionmentioning

confidence: 99%

“…Another impediment to treatment, which is present in MDR cells, involves the sequestration of drugs within cytoplasmic vesicles, followed by drug extrusion out of the cell [7]. Drug sequestration in MDR cells is achieved through the maintenance of abnormally elevated pH gradients across organelle membranes-by the activity of H + -ATPase, an ATP-dependent pump [8,9]. The combination of several mechanisms of drug resistance might complicate chemotherapy and reinforces the need for development of novel drugs and drug formulations effective against drug resistant cancers.…”

Section: Introductionmentioning

confidence: 99%

An essential relationship between ATP depletion and chemosensitizing activity of Pluronic® block copolymers

Kabanov

Batrakova

Alakhov

2003

Journal of Controlled Release

123

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“…MRP also changes the permeability of cell membranes and the pH within cells, both of which are important factors leading to MDR. Furthermore, both p-gp and MRP can alter the sensitivity of drug-resistant cells to chemotherapy by impacting DNA repair activity [16,17].…”

Section: Discussionmentioning

confidence: 99%

Mifepristone regulates the multidrug resistance via miR-758/MEPE of Hela cell lines

Hong¹,

Zhang²,

Liu³

et al. 2020

EJGO

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Background:In cervical cancer, matrix extracellular phosphoglycoprotein (MEPE) plays an important role of multidrug resistance, which is associated with miR-758. Mifepristone has anti-drug resistance effects, but whether mifepristone regulates the expression of multidrug resistance proteins via the pathway mediated by miR-758/MEPE is still unclear. Hela cells were induced by mifepristone (named as Hela/MIF cells). Then, matrix extracellular phosphoglycoprotein siRNA, and miR-758 mimics were transfected into HeLa/MIF cells. The sensitivity, clone forming ability, migration, and level of apoptosis of the cells in each group were respectively measured by CCK-8 assays, clone forming assays, transwell assays, and flow cytometry analysis. The targeting of miR-758 to MEPE was verified by dual-luciferase assay. At last, the expression of MDR-1, MRP-1, and GST-π were detected by qPCR and western blot assays. Results: The induction by mifepristone not only decreased the sensitivity of Hela cells, but also up-regulated the expression of multidrug resistance proteins. On this basis, by increasing the expression of miR-758 or downregulating the expression of MEPE, the expression of multidrug resistance proteins decreased, while the sensitivity of Hela cells to mifepristone were improved and the level of Hela cells proliferation, colony forming, and invasion further decreased. Conclusions: The induction by mifepristone inhibited the proliferation of Hela cells, but the sensitivity of Hela cells increased. The mechanism may depend on the expression of multidrug resistance protein. This study shows that regulating the expression of miR-758 and MEPE can reduce the resistance of Hela cells to mifepristone, enhance the sensitivity, and further improve the inhibitory effect of mifepristone.

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Evidence for Functional Discrimination Between Leukemic Cells Overexpressing Multidrug-Resistance Associated Protein and P-Glycoprotein

Cited by 7 publications

References 20 publications

Polymer genomics: An insight into pharmacology and toxicology of nanomedicines☆

Polymer genomics: An insight into pharmacology and toxicology of nanomedicines☆

An essential relationship between ATP depletion and chemosensitizing activity of Pluronic® block copolymers

Mifepristone regulates the multidrug resistance via miR-758/MEPE of Hela cell lines

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