Effects of Polyphenols on P-Glycoprotein (ABCB1) Activity
P-glycoprotein (Pgp, ABCB1) is a member of one of the largest families of active transporter proteins called ABC transporters. Thanks to its expression in tissues with barrier functions and its broad substrate spectrum, it is an important determinant of the absorption, metabolism and excretion of ma...
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MDPI AG
2021-12-01
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| Online Access: | https://www.mdpi.com/1999-4923/13/12/2062 |
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| author | Kuljeet Singh Szabolcs Tarapcsák Zsuzsanna Gyöngy Zsuzsanna Ritter Gyula Batta Rosevalentine Bosire Judit Remenyik Katalin Goda |
| author_facet | Kuljeet Singh Szabolcs Tarapcsák Zsuzsanna Gyöngy Zsuzsanna Ritter Gyula Batta Rosevalentine Bosire Judit Remenyik Katalin Goda |
| author_sort | Kuljeet Singh |
| collection | DOAJ |
| description | P-glycoprotein (Pgp, ABCB1) is a member of one of the largest families of active transporter proteins called ABC transporters. Thanks to its expression in tissues with barrier functions and its broad substrate spectrum, it is an important determinant of the absorption, metabolism and excretion of many drugs. Pgp and/or some other drug transporting ABC proteins (e.g., ABCG2, MRP1) are overexpressed in nearly all cancers and cancer stem cells by which cancer cells become resistant against many drugs. Thus, Pgp inhibition might be a strategy for fighting against drug-resistant cancer cells. Previous studies have shown that certain polyphenols interact with human Pgp. We tested the effect of 15 polyphenols of sour cherry origin on the basal and verapamil-stimulated ATPase activity of Pgp, calcein-AM and daunorubicin transport as well as on the conformation of Pgp using the conformation sensitive UIC2 mAb. We found that quercetin, quercetin-3-glucoside, narcissoside and ellagic acid inhibited the ATPase activity of Pgp and increased the accumulation of calcein and daunorubicin by Pgp-positive cells. Cyanidin-3O-sophoroside, catechin, naringenin, kuromanin and caffeic acid increased the ATPase activity of Pgp, while they had only a weaker effect on the intracellular accumulation of fluorescent Pgp substrates. Several tested polyphenols including epicatechin, trans-ferulic acid, oenin, malvin and chlorogenic acid were ineffective in all assays applied. Interestingly, catechin and epicatechin behave differently, although they are stereoisomers. We also investigated the effect of quercetin, naringenin and ellagic acid added in combination with verapamil on the transport activity of Pgp. In these experiments, we found that the transport inhibitory effect of the tested polyphenols and verapamil was additive or synergistic. Generally, our data demonstrate diverse interactions of the tested polyphenols with Pgp. Our results also call attention to the potential risks of drug–drug interactions (DDIs) associated with the consumption of dietary polyphenols concurrently with chemotherapy treatment involving Pgp substrate/inhibitor drugs. |
| first_indexed | 2024-03-10T03:19:14Z |
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| id | doaj.art-387776fb4e1142fba4dd2dcfea298dd4 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:19:14Z |
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| series | Pharmaceutics |
| spelling | doaj.art-387776fb4e1142fba4dd2dcfea298dd42023-11-23T10:05:25ZengMDPI AGPharmaceutics1999-49232021-12-011312206210.3390/pharmaceutics13122062Effects of Polyphenols on P-Glycoprotein (ABCB1) ActivityKuljeet Singh0Szabolcs Tarapcsák1Zsuzsanna Gyöngy2Zsuzsanna Ritter3Gyula Batta4Rosevalentine Bosire5Judit Remenyik6Katalin Goda7Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDepartment of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDepartment of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDepartment of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDepartment of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDepartment of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryInstitute of Food Technology, Faculty of Agricultural and Food Sciences and Environmental Management, University of Debrecen, 4032 Debrecen, HungaryDepartment of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryP-glycoprotein (Pgp, ABCB1) is a member of one of the largest families of active transporter proteins called ABC transporters. Thanks to its expression in tissues with barrier functions and its broad substrate spectrum, it is an important determinant of the absorption, metabolism and excretion of many drugs. Pgp and/or some other drug transporting ABC proteins (e.g., ABCG2, MRP1) are overexpressed in nearly all cancers and cancer stem cells by which cancer cells become resistant against many drugs. Thus, Pgp inhibition might be a strategy for fighting against drug-resistant cancer cells. Previous studies have shown that certain polyphenols interact with human Pgp. We tested the effect of 15 polyphenols of sour cherry origin on the basal and verapamil-stimulated ATPase activity of Pgp, calcein-AM and daunorubicin transport as well as on the conformation of Pgp using the conformation sensitive UIC2 mAb. We found that quercetin, quercetin-3-glucoside, narcissoside and ellagic acid inhibited the ATPase activity of Pgp and increased the accumulation of calcein and daunorubicin by Pgp-positive cells. Cyanidin-3O-sophoroside, catechin, naringenin, kuromanin and caffeic acid increased the ATPase activity of Pgp, while they had only a weaker effect on the intracellular accumulation of fluorescent Pgp substrates. Several tested polyphenols including epicatechin, trans-ferulic acid, oenin, malvin and chlorogenic acid were ineffective in all assays applied. Interestingly, catechin and epicatechin behave differently, although they are stereoisomers. We also investigated the effect of quercetin, naringenin and ellagic acid added in combination with verapamil on the transport activity of Pgp. In these experiments, we found that the transport inhibitory effect of the tested polyphenols and verapamil was additive or synergistic. Generally, our data demonstrate diverse interactions of the tested polyphenols with Pgp. Our results also call attention to the potential risks of drug–drug interactions (DDIs) associated with the consumption of dietary polyphenols concurrently with chemotherapy treatment involving Pgp substrate/inhibitor drugs.https://www.mdpi.com/1999-4923/13/12/2062P-glycoprotein (ABCB1)polyphenolsATPase activitytransport activityUIC2 reactivitymembrane fluidity |
| spellingShingle | Kuljeet Singh Szabolcs Tarapcsák Zsuzsanna Gyöngy Zsuzsanna Ritter Gyula Batta Rosevalentine Bosire Judit Remenyik Katalin Goda Effects of Polyphenols on P-Glycoprotein (ABCB1) Activity Pharmaceutics P-glycoprotein (ABCB1) polyphenols ATPase activity transport activity UIC2 reactivity membrane fluidity |
| title | Effects of Polyphenols on P-Glycoprotein (ABCB1) Activity |
| title_full | Effects of Polyphenols on P-Glycoprotein (ABCB1) Activity |
| title_fullStr | Effects of Polyphenols on P-Glycoprotein (ABCB1) Activity |
| title_full_unstemmed | Effects of Polyphenols on P-Glycoprotein (ABCB1) Activity |
| title_short | Effects of Polyphenols on P-Glycoprotein (ABCB1) Activity |
| title_sort | effects of polyphenols on p glycoprotein abcb1 activity |
| topic | P-glycoprotein (ABCB1) polyphenols ATPase activity transport activity UIC2 reactivity membrane fluidity |
| url | https://www.mdpi.com/1999-4923/13/12/2062 |
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