Modulation of the activity of ABC transporters (P-glycoprotein, MRP2, BCRP) by flavonoids and drug response

Alvarez, Ana I.; Real, Rebeca; Pérez, Marcela Mastachi; Mendoza, Gracia; Prieto, J. E.; Merino, Gracia

doi:10.1002/jps.21851

Cited by 197 publications

(164 citation statements)

References 154 publications

(195 reference statements)

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“…Njastad et al (2014) have recently reported that factors such as reconjugation and secretion into the rumen and intestinal wall as well as in cells from the udder could be limiting factors in the content of dietary isoflavones and lignans into milk. ABCG2 has been previously reported to be involved in intestinal conjugation and hepatic metabolism of isoflavones (Alvarez et al, 2010). Furthermore, ABCG2 expression in bovine rumen, intestine, liver and mammary gland has recently been reported Haslam and Simmons, 2014).…”

Section: Enterolactonementioning

confidence: 99%

Effect of bovine ABCG2 polymorphism Y581S SNP on secretion into milk of enterolactone, riboflavin and uric acid

Otero

Miguel

González-Lobato

et al. 2016

animal

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The ATP-binding cassette transporter G2/breast cancer resistance protein (ABCG2/BCRP) is an efflux protein involved in the bioavailability and milk secretion of endogenous and exogenous compounds, actively affecting milk composition. A limited number of physiological substrates have been identified. However, no studies have reported the specific effect of this polymorphism on the secretion into milk of compounds implicated in milk quality such as vitamins or endogenous compounds. The bovine ABCG2 Y581S polymorphism is described as a gain-of-function polymorphism that increases milk secretion and decreases plasma levels of its substrates. This work aims to study the impact of Y581S polymorphism on plasma disposition and milk secretion of compounds such as riboflavin (vitamin B 2 ), enterolactone, a microbiota-derived metabolite from the dietary lignan secoisolariciresinol and uric acid. In vitro transport of these compounds was assessed in MDCK-II cells overexpressing the bovine ABCG2 (WT-bABCG2) and its Y581S variant (Y581S-bABCG2). Plasma and milk levels were obtained from Y/Y homozygous and Y/S heterozygous cows. The results show that riboflavin was more efficiently transported in vitro by the Y581S variant, although no differences were noted in vivo. Both uric acid and enterolactone were substrates in vitro of the bovine ABCG2 variants and were actively secreted into milk with a two-fold increase in the milk/plasma ratio for Y/S with respect to Y/Y cows. The in vitro ABCG2-mediated transport of the drug mitoxantrone, as a model substrate, was inhibited by enterolactone in both variants, suggesting the possible in vivo use of this enterolignan to reduce ABCG2-mediated milk drug transfer in cows. The Y581S variant was inhibited to a lesser extent probably due to its higher transport capacity. All these findings point to a significant role of the ABCG2 Y581S polymorphism in the milk disposition of enterolactone and the endogenous molecules riboflavin and uric acid, which could affect both milk quality and functionality.

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Section: Enterolactonementioning

confidence: 99%

Effect of bovine ABCG2 polymorphism Y581S SNP on secretion into milk of enterolactone, riboflavin and uric acid

Otero

Miguel

González-Lobato

et al. 2016

animal

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“…For example, the flavonoids apigenin, kaempferol, and quercetin which are constituents of Ginkgo biloba formulations, onions, strawberries, and apples [2] were characterized by inhibition and/or induction of CYP3A4, ABCB1, and ABCC2 [6][7].…”

Section: Introductionmentioning

confidence: 99%

Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1

Mandery

Bujok

Schmidt

et al. 2010

Biochemical Pharmacology

121

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Influence of the flavonoids apigenin; kaempferol and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1, Biochemical Pharmacology (2010), doi:10.1016/j.bcp.2010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 37 A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 4 modification of OATP1A2 and OATP2B1 transport activity by apigenin, kaempferol, and quercetin may be a mechanism for food-drug or drug-drug interactions in humans.Page 5 of 37A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 A c c e p t e d M a n u s c r i p t Generation of a HEK293 cell line stably expressing OATP1A2The SLCO1A2 coding sequence (NM_134431. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 10 subcloned into the retroviral vector pQCXIN (Takara Bio Europe/Clontech, SaintGermain-en-Laye, France). Human embryonic kidney cells (HEK293) were transfected with the plasmid pQCXIN-OATP1A2 using a retroviral gene transfer and expression kit (Takara Bio Europe/Clontech, Saint-Germain-en-Laye, France). After geneticin (G-418; 500 µg/ml) treatment, single colonies were selected and characterized for OATP1A2 mRNA and protein expression using ...

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“…Among them are the flavonoids which are polyphenolic compounds found in foods and herbal products. Different flavonoids are potent modulators of ABC transporters: kaempferol, apigenin and myricetin are inhibitors of MRP1 [218] , kaempferide, quercetin, diosmin and glabridin are inhibitors of P-gp [219] and silymarin, hesperetin and daidzein are inhibitors of ABCG2 [220] . The bioflavonoids neochamaejasmin B (NCB) [221] and chamaechromone from the root of Stellera chamaejasme L. are able to inhibit the expression and activity of MRP1.…”

Section: Inhibitors From Natural Sourcesmentioning

confidence: 99%

“…Furthermore NCB and chamaechromone co-administration increased chamaechromone bioavailability substantially [166] . However, further investigation is needed to define optimal dose schedules of flavonoids capable of inducing ABC transporter inhibition [219] . Future studies would also have to take into account flavonoid pharmacokinetics, bioavailability and activity of flavonoid metabolites after ingestion, which would reduce active flavonoid plasma concentrations [222,223] .…”

Section: Inhibitors From Natural Sourcesmentioning

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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Modulation of the activity of ABC transporters (P-glycoprotein, MRP2, BCRP) by flavonoids and drug response

Cited by 197 publications

References 154 publications

Effect of bovine ABCG2 polymorphism Y581S SNP on secretion into milk of enterolactone, riboflavin and uric acid

Effect of bovine ABCG2 polymorphism Y581S SNP on secretion into milk of enterolactone, riboflavin and uric acid

Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1

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

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