Evaluation of dual P-gp-BCRP inhibitors as nanoparticle formulation

Singh, Manu Smriti; Juvale, Kapil; Wiese, Michael; Lamprecht, Alf

doi:10.1016/j.ejps.2015.04.027

Cited by 19 publications

(25 citation statements)

References 22 publications

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“…Calcein acetoxymethyl AM ester, a fluorescent dye and substrate for P‐gp efflux pump, was used to evaluate the functional activity and efflux pattern of P‐gp in TN MDA‐MB‐231, in presence of 20 and 50 μM rutin (Singh et al , ). Treatment with Verapamil hydrochloride, a well‐known P‐gp inhibitor, was performed as positive control for this assay.…”

Section: Methodsmentioning

confidence: 99%

Rutin, a Quercetin Glycoside, Restores Chemosensitivity in Human Breast Cancer Cells

Iriti

Kubina

Cochis

et al. 2017

Phytotherapy Research

140

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Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate-binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3-O-β-d-rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB-MDA-231, selected as representative for triple-negative breast cancer and (ii) MCF-7 used as a well-characterized model of HER2-negative breast cancer. To assess the cytocompatibility of rutin against non-cancer cells, primary human mammary fibroblasts were used as control and non-target cells. In MDA-MB-231 cells, 20 μM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p < 0.05) increased the anticancer activity of both chemotherapeutics, at 24-48-72 h, and decreased the activity of the adenosine triphosphate-binding cassette transporters, namely, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Flow cytometry analysis showed 20 μM and 50 μM rutin arrested cell cycle at G2/M and G0/G1 phases, respectively, significantly promoting cell apoptosis. Rutin, via non-selective inhibition of P-gp and BCRP pumps, efficiently reverses multidrug resistance and restores chemosensitivity to cyclophosphamide and cyclophosphamide of human chemoresistant, triple-negative breast cancer cells, successfully arresting cell cycle progression. Copyright © 2017 John Wiley & Sons, Ltd.

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Section: Methodsmentioning

confidence: 99%

Rutin, a Quercetin Glycoside, Restores Chemosensitivity in Human Breast Cancer Cells

Iriti

Kubina

Cochis

et al. 2017

Phytotherapy Research

140

View full text Add to dashboard Cite

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“…An enormous amount of work has been dedicated to identifying druggable targets that will halt the proliferation of MDR cells (reviewed in [ 104 , 105 ]). Reasonably, much of the work has focused on developing inhibitors against the drug efflux pumps MDR-1 and BCRP, which show promise against breast and other cancers in vitro [ 106 , 107 , 108 ]. Studies using mouse models where ABC transporters are inhibited are also beginning to show promise as a reversal strategy [ 109 , 110 , 111 ].…”

Section: Reversal Of Mdrmentioning

confidence: 99%

Development, Maintenance, and Reversal of Multiple Drug Resistance: At the Crossroads of TFPI1, ABC Transporters, and HIF1

Arnason

Harkness

2015

Cancers

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Early detection and improved therapies for many cancers are enhancing survival rates. Although many cytotoxic therapies are approved for aggressive or metastatic cancer; response rates are low and acquisition of de novo resistance is virtually universal. For decades; chemotherapeutic treatments for cancer have included anthracyclines such as Doxorubicin (DOX); and its use in aggressive tumors appears to remain a viable option; but drug resistance arises against DOX; as for all other classes of compounds. Our recent work suggests the anticoagulant protein Tissue Factor Pathway Inhibitor 1α (TFPI1α) plays a role in driving the development of multiple drug resistance (MDR); but not maintenance; of the MDR state. Other factors; such as the ABC transporter drug efflux pumps MDR-1/P-gp (ABCB1) and BCRP (ABCG2); are required for MDR maintenance; as well as development. The patient population struggling with therapeutic resistance specifically requires novel treatment options to resensitize these tumor cells to therapy. In this review we discuss the development, maintenance, and reversal of MDR as three distinct phases of cancer biology. Possible means to exploit these stages to reverse MDR will be explored. Early molecular detection of MDR cancers before clinical failure has the potential to offer new approaches to fighting MDR cancer.

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“…Similarly, nanoparticle drug delivery using polyethyleneimine as a carrier for siRNA has been reported to down-regulate ABCG2 and decrease the mitoxantrone IC (50) values by approximately 14-fold [86] . Other efforts to deliver ABCG2 and P-gp inhibitors with nanoparticles show complete reversal of resistance in ABCG2 positive MDR cells [199] .…”

Section: Abcg2 Inhibitorsmentioning

confidence: 99%

“…Such dual inhibitors will be effective in cases where both transporters participate in MDR and the cytotoxic drug is a substrate of both transporters. Conceivably, [86,198,199] siRNA siRNA delivered by nanoparticles…”

Section: Dual Inhibitorsmentioning

confidence: 99%

How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance?

Jaramillo¹,

Saig²,

Cloos³

et al. 2018

CDR

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P-glycoprotein (ABCB1), multidrug resistance protein-1 (ABCC1) and breast cancer resistance protein (ABCG2) belong to the ATP-binding cassette (ABC) superfamily of proteins that play an important physiological role in protection of the body from toxic xenobiotics and endogenous metabolites. Beyond this, these transporters determine the toxicity profile of many drugs, and confer multidrug resistance (MDR) in cancer cells associated with a poor treatment outcome of cancer patients.It has long been hypothesized that inhibition of ABC drug efflux transporters will increase drug accumulation and thereby overcome MDR, but until now no approved inhibitor of these transporters is available in the clinic. In this review we present molecular strategies to overcome this type of drug resistance and discuss for each of these strategies their promising value or indicate underlying reasons for their limited success.

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Evaluation of dual P-gp-BCRP inhibitors as nanoparticle formulation

Cited by 19 publications

References 22 publications

Rutin, a Quercetin Glycoside, Restores Chemosensitivity in Human Breast Cancer Cells

Rutin, a Quercetin Glycoside, Restores Chemosensitivity in Human Breast Cancer Cells

Development, Maintenance, and Reversal of Multiple Drug Resistance: At the Crossroads of TFPI1, ABC Transporters, and HIF1

How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance?

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