{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T21:54:18Z","timestamp":1778363658448,"version":"3.51.4"},"reference-count":148,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,3,25]],"date-time":"2023-03-25T00:00:00Z","timestamp":1679702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Portuguese Science and Technology Foundation (FCT)","doi-asserted-by":"publisher","award":["UIDB\/04033\/2020 (CITAB)"],"award-info":[{"award-number":["UIDB\/04033\/2020 (CITAB)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Science and Technology Foundation (FCT)","doi-asserted-by":"publisher","award":["SFRH\/BD\/145855\/2019"],"award-info":[{"award-number":["SFRH\/BD\/145855\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NORTE 2020","award":["UIDB\/04033\/2020 (CITAB)"],"award-info":[{"award-number":["UIDB\/04033\/2020 (CITAB)"]}]},{"name":"NORTE 2020","award":["SFRH\/BD\/145855\/2019"],"award-info":[{"award-number":["SFRH\/BD\/145855\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoX"],"abstract":"<jats:p>The role of intestinal barrier homeostasis in an individual\u2019s general well-being has been widely addressed by the scientific community. Colorectal cancer is among the illnesses that most affect this biological barrier. While chemotherapy is the first choice to treat this type of cancer, multidrug resistance (MDR) is the major setback against the commonly used drugs, with the ATP-binding cassette transporters (ABC transporters) being the major players. The role of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), or breast cancer resistance protein (ABCG2) in the efflux of chemotherapeutic drugs is well described in cancer cells, highlighting these proteins as interesting druggable targets to reverse MDR, decrease drug dosage, and consequently undesired toxicity. Natural products, especially phytochemicals, have a wide diversity of chemical structures, and some particular classes, such as phenolic acids, flavonoids, or pentacyclic triterpenoids, have been reported as inhibitors of P-gp, MRP1, and ABCG2, being able to sensitize cancer cells to chemotherapy drugs. Nevertheless, ABC transporters play a vital role in the cell\u2019s defense against xenobiotics, and some phytochemicals have also been shown to induce the transporters\u2019 activity. A balance must be obtained between xenobiotic efflux in non-tumor cells and bioaccumulation of chemotherapy drugs in cancer cells, in which ABC transporters are essential and natural products play a pivotal role that must be further analyzed. This review summarizes the knowledge concerning the nomenclature and function of ABC-transporters, emphasizing their role in the intestinal barrier cells. In addition, it also focuses on the role of natural products commonly found in food products, e.g., phytochemicals, as modulators of ABC-transporter activity and expression, which are promising nutraceutical molecules to formulate new drug combinations to overcome multidrug resistance.<\/jats:p>","DOI":"10.3390\/jox13020014","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T04:31:21Z","timestamp":1679891481000},"page":"172-192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Natural Products as a Tool to Modulate the Activity and Expression of Multidrug Resistance Proteins of Intestinal Barrier"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1564-3661","authenticated-orcid":false,"given":"Carlos","family":"Martins-Gomes","sequence":"first","affiliation":[{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal"},{"name":"Department of Biology and Environment, School of Life Sciences and Environment, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7524-9914","authenticated-orcid":false,"given":"Am\u00e9lia M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal"},{"name":"Department of Biology and Environment, School of Life Sciences and Environment, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1136\/gut.52.5.759","article-title":"Multidrug resistance 1 gene (P-glycoprotein 170): An important determinant in gastrointestinal disease?","volume":"52","author":"Ho","year":"2003","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"114615","DOI":"10.1016\/j.addr.2022.114615","article-title":"Penetration and translocation of functional inorganic nanomaterials into biological barriers","volume":"191","author":"Cong","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"24020","DOI":"10.1074\/jbc.R114.583658","article-title":"Molecular mechanisms of cellular cholesterol efflux","volume":"289","author":"Phillips","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1002\/prot.26406","article-title":"Plastic structures for diverse substrates: A revisit of human ABC transporters","volume":"90","author":"Hou","year":"2022","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_5","unstructured":"Godbey, W.T. (2014). An Introduction to Biotechnology, Woodhead Publishing."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1111\/brv.12702","article-title":"ATP binding cassette importers in eukaryotic organisms","volume":"96","author":"Choi","year":"2021","journal-title":"Biol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bukowski, K., Kciuk, M., and Kontek, R. (2020). Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093233"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Aires, V., Colin, D.J., Doreau, A., Di Pietro, A., Heydel, J.-M., Artur, Y., Latruffe, N., and Delmas, D. (2019). P-Glycoprotein 1 Affects Chemoactivities of Resveratrol against Human Colorectal Cancer Cells. Nutrients, 11.","DOI":"10.3390\/nu11092098"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1016\/j.addr.2013.09.018","article-title":"Multidrug resistance: Physiological principles and nanomedical solutions","volume":"65","author":"Kunjachan","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/s41568-018-0005-8","article-title":"Revisiting the role of ABC transporters in multidrug-resistant cancer","volume":"18","author":"Robey","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.5732\/cjc.011.10466","article-title":"Role of ABC transporters in cancer chemotherapy","volume":"31","author":"Sun","year":"2012","journal-title":"Chin. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/jcp.1040830114","article-title":"Reduced permeability in CHO cells as a mechanism of resistance to colchicine","volume":"83","author":"Ling","year":"1974","journal-title":"J. Cell. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/0005-2736(76)90160-7","article-title":"A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants","volume":"455","author":"Juliano","year":"1976","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Biomembr."},{"key":"ref_14","first-page":"4413","article-title":"Daunorubicin-resistant Chinese hamster ovary cells expressing multidrug resistance and a cell-surface P-glycoprotein","volume":"43","author":"Kartner","year":"1983","journal-title":"Cancer Res."},{"key":"ref_15","first-page":"515","article-title":"Cross-resistance of vinblastine- and taxol-resistant mutants of Chinese hamster ovary cells to other anticancer drugs","volume":"69","author":"Gupta","year":"1985","journal-title":"Cancer Treat. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"426","DOI":"10.3109\/10409238.2014.953626","article-title":"Diversity in ABC transporters: Type I, II and III importers","volume":"49","author":"Rice","year":"2014","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1085\/jgp.201411164","article-title":"Structural diversity of ABC transporters","volume":"143","author":"Guskov","year":"2014","journal-title":"J. Gen. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1146\/annurev-biochem-011520-105201","article-title":"Structural and Mechanistic Principles of ABC Transporters","volume":"89","author":"Thomas","year":"2020","journal-title":"Annu. Rev. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1021\/acscentsci.7b00068","article-title":"Unidirectional Transport Mechanism in an ATP Dependent Exporter","volume":"3","author":"Xu","year":"2017","journal-title":"ACS Cent. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1002\/1873-3468.13935","article-title":"Structural and functional diversity calls for a new classification of ABC transporters","volume":"594","author":"Thomas","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_21","first-page":"590","article-title":"Antibiotic Resistance Mediated by the MacB ABC Transporter Family: A Structural and Functional Perspective","volume":"9","author":"Greene","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1186\/1479-7364-3-3-281","article-title":"Human ATP-binding cassette (ABC) transporter family","volume":"3","author":"Vasiliou","year":"2009","journal-title":"Hum. Genom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1002\/1873-3468.13997","article-title":"The role of the degenerate nucleotide binding site in type I ABC exporters","volume":"594","author":"Stockner","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.tibs.2018.11.003","article-title":"Control of mRNA Translation by Versatile ATP-Driven Machines","volume":"44","author":"Gerovac","year":"2019","journal-title":"Trends Biochem. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3412074","DOI":"10.1155\/2018\/3412074","article-title":"Overcoming P-Glycoprotein-Mediated Multidrug Resistance in Colorectal Cancer: Potential Reversal Agents among Herbal Medicines","volume":"2018","author":"Lee","year":"2018","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/jps.21851","article-title":"Modulation of the activity of ABC transporters (P-glycoprotein, MRP2, BCRP) by flavonoids and drug response","volume":"99","author":"Alvarez","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/s41594-019-0280-4","article-title":"Mechanics and pharmacology of substrate selection and transport by eukaryotic ABC exporters","volume":"26","author":"Srikant","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jones, P.M., and George, A.M. (2023). The Switch and Reciprocating Models for the Function of ABC Multidrug Exporters: Perspectives on Recent Research. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032624"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s40262-020-00867-1","article-title":"Effect of P-glycoprotein (P-gp) Inducers on Exposure of P-gp Substrates: Review of Clinical Drug\u2013Drug Interaction Studies","volume":"59","author":"Elmeliegy","year":"2020","journal-title":"Clin. Pharmacokinet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.biopha.2017.01.053","article-title":"Anticancer activity of baicalein and luteolin studied in colorectal adenocarcinoma LoVo cells and in drug-resistant LoVo\/Dx cells","volume":"88","author":"Uryga","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1126\/science.1360704","article-title":"Overexpression of a Transporter Gene in a Multidrug-Resistant Human Lung Cancer Cell Line","volume":"258","author":"Cole","year":"1992","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0005-2736(99)00167-4","article-title":"The multidrug resistance protein family","volume":"1461","author":"Borst","year":"1999","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Biomembr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0304-3835(00)00646-7","article-title":"Analysis of the structure and expression pattern of MRP7 (ABCC10), a new member of the MRP subfamily","volume":"162","author":"Hopper","year":"2001","journal-title":"Cancer Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.neuroscience.2005.10.025","article-title":"Human multidrug resistance protein 8 (MRP8\/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system","volume":"137","author":"Bortfeld","year":"2006","journal-title":"Neuroscience"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6997","DOI":"10.1073\/pnas.102187299","article-title":"MRP9, an unusual truncated member of the ABC transporter superfamily, is highly expressed in breast cancer","volume":"99","author":"Iavarone","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"58","DOI":"10.5732\/cjc.011.10329","article-title":"Multidrug resistance associated proteins in multidrug resistance","volume":"31","author":"Sodani","year":"2012","journal-title":"Chin. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1146\/annurev-pharmtox-011613-135959","article-title":"Targeting multidrug resistance protein 1 (MRP1, ABCC1): Past, present, and future","volume":"54","author":"Cole","year":"2014","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1038\/sj.onc.1206953","article-title":"The MRP family of drug efflux pumps","volume":"22","author":"Kruh","year":"2003","journal-title":"Oncogene"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"439","DOI":"10.2174\/092986711794839197","article-title":"Structural and functional properties of human multidrug resistance protein 1 (MRP1\/ABCC1)","volume":"18","author":"He","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.3892\/ol.2017.5741","article-title":"The role of MRP1 in the multidrug resistance of colorectal cancer","volume":"13","author":"Cao","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s12038-016-9601-5","article-title":"ABCG2 inhibition as a therapeutic approach for overcoming multidrug resistance in cancer","volume":"41","author":"Hasanabady","year":"2016","journal-title":"J. Biosci."},{"key":"ref_42","first-page":"1","article-title":"Human ABCG2: Structure, function, and its role in multidrug resistance","volume":"3","author":"Mo","year":"2012","journal-title":"Int. J. Biochem. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1080\/10409238.2021.1925217","article-title":"Cholesterol efflux pathways, inflammation, and atherosclerosis","volume":"56","author":"Groenen","year":"2021","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.canlet.2019.03.011","article-title":"ABCG1 and Pgp identify drug resistant, self-renewing osteosarcoma cells","volume":"453","author":"Roundhill","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1309\/LMO485SPYXBQANXJ","article-title":"ABCA1 and ABCG1 Expression in the Small Intestine of Type 2 Diabetic Rats","volume":"45","author":"Lou","year":"2014","journal-title":"Lab. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1006\/bbrc.2001.5130","article-title":"Functional Characterization of the Human Multidrug Transporter, ABCG2, Expressed in Insect Cells","volume":"285","author":"Litman","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1016\/j.foodchem.2012.12.021","article-title":"Identification of novel dietary phytochemicals inhibiting the efflux transporter breast cancer resistance protein (BCRP\/ABCG2)","volume":"138","author":"Tan","year":"2013","journal-title":"Food Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1006\/geno.1994.1237","article-title":"Cloning of Two Novel ABC Transporters Mapping on Human Chromosome 9","volume":"21","author":"Luciani","year":"1994","journal-title":"Genomics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.cell.2017.05.020","article-title":"Structure of the Human Lipid Exporter ABCA1","volume":"169","author":"Qian","year":"2017","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.dsx.2019.03.004","article-title":"ABCA1 and metabolic syndrome; a review of the ABCA1 role in HDL-VLDL production, insulin-glucose homeostasis, inflammation and obesity","volume":"13","author":"Babashamsi","year":"2019","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_51","first-page":"522","article-title":"Regulation of ABCA1 functions by signaling pathways","volume":"1821","author":"Liu","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1002\/iub.1955","article-title":"Vitamin E intestinal absorption: Regulation of membrane transport across the enterocyte","volume":"71","author":"Reboul","year":"2019","journal-title":"IUBMB Life"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3390\/biology4010017","article-title":"Will Lipidation of ApoA1 through Interaction with ABCA1 at the Intestinal Level Affect the Protective Functions of HDL?","volume":"4","author":"Niesor","year":"2015","journal-title":"Biology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1002\/1878-0261.12367","article-title":"ABCA1 overexpression worsens colorectal cancer prognosis by facilitating tumour growth and caveolin-1-dependent invasiveness, and these effects can be ameliorated using the BET inhibitor apabetalone","volume":"12","author":"Feliu","year":"2018","journal-title":"Mol. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0167-4889(01)00175-6","article-title":"Inhibition of the multidrug resistance P-glycoprotein activity by green tea polyphenols","volume":"1542","author":"Jodoin","year":"2002","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"111827","DOI":"10.1016\/j.fct.2020.111827","article-title":"Natural P-gp inhibitor EGCG improves the acteoside absorption in Caco-2 cell monolayers and increases the oral bioavailability of acteoside in rats","volume":"146","author":"Zhou","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1211\/0022357044003","article-title":"Inhibition of P-glycoprotein function by tea catechins in KB-C2 cells","volume":"56","author":"Kitagawa","year":"2004","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1167.6","DOI":"10.1096\/fasebj.27.1_supplement.1167.6","article-title":"Effect of EGCG on the expression and activity of P-glycoprotein in breast cancer cells","volume":"27","author":"Morales","year":"2013","journal-title":"FASEB J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1021\/acs.jafc.8b06665","article-title":"(\u2212)-Epigallocatechin Gallate (EGCG) Enhances the Sensitivity of Colorectal Cancer Cells to 5-FU by Inhibiting GRP78\/NF-\u03baB\/miR-155-5p\/MDR1 Pathway","volume":"67","author":"La","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"103553","DOI":"10.1016\/j.jff.2019.103553","article-title":"EGCG maintained Nrf2-mediated redox homeostasis and minimized etoposide resistance in lung cancer cells","volume":"62","author":"Datta","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/ptr.5990","article-title":"Epigallocatechin-3-gallate enhances differentiation of acute promyelocytic leukemia cells via inhibition of PML-RAR\u03b1 and HDAC1","volume":"32","author":"Moradzadeh","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1186\/s40064-016-3267-1","article-title":"Natural flavonoids silymarin and quercetin improve the brain distribution of co-administered P-gp substrate drugs","volume":"5","author":"Khurana","year":"2016","journal-title":"SpringerPlus"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1002\/ptr.6081","article-title":"Quercetin reversed MDR in breast cancer cells through down-regulating P-gp expression and eliminating cancer stem cells mediated by YB-1 nuclear translocation","volume":"32","author":"Li","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.bcp.2007.04.002","article-title":"The effect of quercetin phase II metabolism on its MRP1 and MRP2 inhibiting potential","volume":"74","author":"Vaessen","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Mohos, V., Flisz\u00e1r-Ny\u00fal, E., Ungv\u00e1ri, O., Kuffa, K., Needs, P.W., Kroon, P.A., Telbisz, \u00c1., \u00d6zvegy-Laczka, C., and Po\u00f3r, M. (2020). Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters. Nutrients, 12.","DOI":"10.3390\/nu12082306"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"428","DOI":"10.3892\/or.2016.4813","article-title":"Ursolic acid inhibits proliferation and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hypoxia-inducible factor-1\u03b1 in vitro","volume":"36","author":"Wang","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S1001-9294(16)30004-9","article-title":"Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of Rosuvastatin In Vivo and Vitro","volume":"30","author":"Wen","year":"2015","journal-title":"Chin. Med. Sci. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.phrs.2009.11.010","article-title":"Inhibition of anticancer drug efflux transporter P-glycoprotein by rosemary phytochemicals","volume":"61","author":"Nabekura","year":"2010","journal-title":"Pharmacol. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/cas.13425","article-title":"Ursolic acid enhances the therapeutic effects of oxaliplatin in colorectal cancer by inhibition of drug resistance","volume":"109","author":"Zhang","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.jnutbio.2013.12.003","article-title":"Oleanolic and maslinic acid sensitize soft tissue sarcoma cells to doxorubicin by inhibiting the multidrug resistance protein MRP-1, but not P-glycoprotein","volume":"25","author":"Villar","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.canlet.2006.06.008","article-title":"Oleanolic acid inhibits the activity of the multidrug resistance protein ABCC1 (MRP1) but not of the ABCB1 (P-glycoprotein): Possible use in cancer chemotherapy","volume":"248","author":"Braga","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1124\/dmd.110.035212","article-title":"The Bioflavonoid Kaempferol Is an Abcg2 Substrate and Inhibits Abcg2-Mediated Quercetin Efflux","volume":"39","author":"An","year":"2011","journal-title":"Drug Metab. Dispos."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.bbrc.2004.12.081","article-title":"Effects of dietary chemopreventive phytochemicals on P-glycoprotein function","volume":"327","author":"Nabekura","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Liu, C.-M., Kao, C.-L., Tseng, Y.-T., Lo, Y.-C., and Chen, C.-Y. (2017). Ginger Phytochemicals Inhibit Cell Growth and Modulate Drug Resistance Factors in Docetaxel Resistant Prostate Cancer Cell. Molecules, 22.","DOI":"10.3390\/molecules22091477"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Zhou, Q., Ye, M., Lu, Y., Zhang, H., Chen, Q., Huang, S., and Su, S. (2015). Curcumin Improves the Tumoricidal Effect of Mitomycin C by Suppressing ABCG2 Expression in Stem Cell-Like Breast Cancer Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136694"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.7314\/APJCP.2014.15.3.1403","article-title":"Reversal of resistance towards cisplatin by curcumin in cervical cancer cells","volume":"15","author":"Roy","year":"2014","journal-title":"Asian Pac. J. Cancer Prev. APJCP"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.ijpharm.2008.03.010","article-title":"Curcuma drugs and curcumin regulate the expression and function of P-gp in Caco-2 cells in completely opposite ways","volume":"358","author":"Hou","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.taap.2016.06.030","article-title":"P-gp, MRP2 and OAT1\/OAT3 mediate the drug-drug interaction between resveratrol and methotrexate","volume":"306","author":"Jia","year":"2016","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.phymed.2018.06.046","article-title":"Resveratrol mediated cancer cell apoptosis, and modulation of multidrug resistance proteins and metabolic enzymes","volume":"55","author":"Eid","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.bbrc.2010.03.147","article-title":"Resveratrol-mediated reversal of doxorubicin resistance in acute myeloid leukemia cells via downregulation of MRP1 expression","volume":"395","author":"Kweon","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Shankar, S., Nall, D., Tang, S.-N., Meeker, D., Passarini, J., Sharma, J., and Srivastava, R.K. (2011). Resveratrol Inhibits Pancreatic Cancer Stem Cell Characteristics in Human and KrasG12D Transgenic Mice by Inhibiting Pluripotency Maintaining Factors and Epithelial-Mesenchymal Transition. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016530"},{"key":"ref_82","first-page":"105","article-title":"Epidemiology of colorectal cancer","volume":"7","author":"Marley","year":"2016","journal-title":"Int. J. Mol. Epidemiol. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4667","DOI":"10.18203\/2320-6012.ijrms20174914","article-title":"Colorectal cancer: A review","volume":"5","year":"2017","journal-title":"Int. J. Res. Med. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s13304-016-0359-y","article-title":"Worldwide burden of colorectal cancer: A review","volume":"68","author":"Favoriti","year":"2016","journal-title":"Updat. Surg."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s11655-020-3425-8","article-title":"Combating Drug Resistance in Colorectal Cancer Using Herbal Medicines","volume":"27","author":"Lee","year":"2021","journal-title":"Chin. J. Integr. Med."},{"key":"ref_86","unstructured":"Aniogo, E., George, B.P., and Abrahamse, H. (2020). Phytomedicine: Research and Development, CRC Press."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1080\/01635581.2015.1002624","article-title":"Natural Product Modulators to Overcome Multidrug Resistance in Cancer","volume":"67","author":"Cort","year":"2015","journal-title":"Nutr. Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Costea, T., Vlad, O.C., Miclea, L.-C., Ganea, C., Sz\u00f6ll\u0151si, J., and Mocanu, M.-M. (2020). Alleviation of Multidrug Resistance by Flavonoid and Non-Flavonoid Compounds in Breast, Lung, Colorectal and Prostate Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020401"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1211\/002235702603","article-title":"The effect of food components on the absorption of P-gp substrates: A review","volume":"55","author":"Deferme","year":"2003","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4444","DOI":"10.1002\/jps.23753","article-title":"Bitter Melon Extracts Enhance the Activity of Chemotherapeutic Agents Through the Modulation of Multiple Drug Resistance","volume":"102","author":"Kwatra","year":"2013","journal-title":"J. Pharm. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Ben Toumia, I., Sobeh, M., Ponassi, M., Banelli, B., Dameriha, A., Wink, M., Chekir Ghedira, L., and Rosano, C. (2020). A Methanol Extract of Scabiosa atropurpurea Enhances Doxorubicin Cytotoxicity against Resistant Colorectal Cancer Cells In Vitro. Molecules, 25.","DOI":"10.3390\/molecules25225265"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.phrs.2013.03.010","article-title":"Antitumor effect of 5-fluorouracil is enhanced by rosemary extract in both drug sensitive and resistant colon cancer cells","volume":"72","author":"Molina","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1038\/sj.bjp.0704399","article-title":"Saint John\u2019s wort: An in vitro analysis of P-glycoprotein induction due to extended exposure","volume":"134","author":"Perloff","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_94","first-page":"203","article-title":"Comparison of cancer cells in 2D vs. 3D culture reveals differences in AKT\u2013mTOR\u2013S6K signaling and drug responses","volume":"130","author":"Riedl","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1631\/jzus.B1600266","article-title":"Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1\u03b1","volume":"17","author":"Shan","year":"2016","journal-title":"J. Zhejiang Univ.\u2014Sci. B"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Zhou, J.-X., and Wink, M. (2018). Reversal of Multidrug Resistance in Human Colon Cancer and Human Leukemia Cells by Three Plant Extracts and Their Major Secondary Metabolites. Medicines, 5.","DOI":"10.3390\/medicines5040123"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.jff.2018.02.012","article-title":"Chemical characterization and bioactive properties of decoctions and hydroethanolic extracts of Thymus carnosus Boiss","volume":"43","author":"Taghouti","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1039\/C8FO00456K","article-title":"Thymus pulegioides L. as a rich source of antioxidant, anti-proliferative and neuroprotective phenolic compounds","volume":"9","author":"Taghouti","year":"2018","journal-title":"Food Funct."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.indcrop.2017.08.054","article-title":"Phenological changes in triterpenic and phenolic composition of Thymus L. species","volume":"109","author":"Raudone","year":"2017","journal-title":"Ind. Crops Prod."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.foodchem.2012.07.091","article-title":"Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity","volume":"136","author":"Kontogianni","year":"2013","journal-title":"Food Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jpba.2018.04.014","article-title":"\u03b1-Glucosidase enzyme inhibitory effects and ursolic and oleanolic acid contents of fourteen Anatolian Salvia species","volume":"155","author":"Dirmenci","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1002\/tox.22544","article-title":"Lupeol alters ER stress-signaling pathway by downregulating ABCG2 expression to induce Oxaliplatin-resistant LoVo colorectal cancer cell apoptosis","volume":"33","author":"Chen","year":"2018","journal-title":"Environ. Toxicol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/j.phymed.2014.06.013","article-title":"Reversal of P-glycoprotein (P-gp) mediated multidrug resistance in colon cancer cells by cryptotanshinone and dihydrotanshinone of Salvia miltiorrhiza","volume":"21","author":"Hu","year":"2014","journal-title":"Phytomedicine"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"555","DOI":"10.3892\/etm.2011.441","article-title":"Tanshinone IIA potentiates the efficacy of 5-FU in Colo205 colon cancer cells in vivo through downregulation of P-gp and LC3-II","volume":"3","author":"Su","year":"2012","journal-title":"Exp. Ther. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ejmech.2017.06.047","article-title":"Natural alkaloids as P-gp inhibitors for multidrug resistance reversal in cancer","volume":"138","author":"Joshi","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_106","first-page":"1323","article-title":"Salvianolic acid B reverses multidrug resistance in nude mice bearing human colon cancer stem cells","volume":"18","author":"Guo","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"724","DOI":"10.3892\/mmr.2016.6049","article-title":"Salvianolic acid B reverses multidrug resistance in HCT-8\/VCR human colorectal cancer cells by increasing ROS levels","volume":"15","author":"Guo","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"9499","DOI":"10.1007\/s13277-015-3636-3","article-title":"Resveratrol induces AMPK-dependent MDR1 inhibition in colorectal cancer HCT116\/L-OHP cells by preventing activation of NF-\u03baB signaling and suppressing cAMP-responsive element transcriptional activity","volume":"36","author":"Wang","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_109","first-page":"18","article-title":"Rosmarinic acid, the active component of Salvia miltiorrhizae, improves gliquidone transport by regulating the expression and function of P-gp and BCRP in Caco-2 cells","volume":"75","author":"Li","year":"2020","journal-title":"Die Pharm.\u2014Int. J. Pharm. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2016.07.021","article-title":"Spica prunellae and its marker compound rosmarinic acid induced the expression of efflux transporters through activation of Nrf2-mediated signaling pathway in HepG2 cells","volume":"193","author":"Wu","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"590","DOI":"10.3109\/03602531003758690","article-title":"Interactions of dietary phytochemicals with ABC transporters: Possible implications for drug disposition and multidrug resistance in cancer","volume":"42","author":"Li","year":"2010","journal-title":"Drug Metab. Rev."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/0006-2952(94)90568-1","article-title":"Modulation of adriamycin\u00ae accumulation and efflux by flavonoids in HCT-15 colon cells: Activation of P-glycoprotein as a putative mechanism","volume":"48","author":"Critchfield","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/mnfr.200600225","article-title":"Flavonoids alter P-gp expression in intestinal epithelial cells in vitro and in vivo","volume":"51","author":"Lohner","year":"2007","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1089\/jmf.2011.1845","article-title":"The Role of Turmerones on Curcumin Transportation and P-Glycoprotein Activities in Intestinal Caco-2 Cells","volume":"15","author":"Yue","year":"2011","journal-title":"J. Med. Food"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/s11655-018-2997-z","article-title":"Curcumin Reverses 5-Fluorouracil Resistance by Promoting Human Colon Cancer HCT-8\/5-FU Cell Apoptosis and Down-regulating Heat Shock Protein 27 and P-Glycoprotein","volume":"25","author":"He","year":"2019","journal-title":"Chin. J. Integr. Med."},{"key":"ref_116","first-page":"1","article-title":"Mechanism of reversal of multidrug resistance by curcumin in human colorectal cancer cell line HCT-8\/5-FU","volume":"16","author":"Fan","year":"2017","journal-title":"Genet. Mol. Res. GMR"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"114129","DOI":"10.1016\/j.jpba.2021.114129","article-title":"Curcumin reverses doxorubicin resistance in colon cancer cells at the metabolic level","volume":"201","author":"Zhang","year":"2021","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_118","first-page":"313","article-title":"Curcumin Regulates Colon Cancer by Inhibiting P-Glycoprotein in In-situ Cancerous Colon Perfusion Rat Model","volume":"5","author":"Neerati","year":"2013","journal-title":"J. Cancer Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"173185","DOI":"10.1016\/j.ejphar.2020.173185","article-title":"Quercetin overcomes colon cancer cells resistance to chemotherapy by inhibiting solute carrier family 1, member 5 transporter","volume":"881","author":"Zhou","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.3892\/or.2017.5410","article-title":"Reversal of P-gp-mediated multidrug resistance in colon cancer by cinobufagin","volume":"37","author":"Yuan","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"48012","DOI":"10.18632\/oncotarget.18225","article-title":"Bufalin reverses ABCB1-mediated drug resistance in colorectal cancer","volume":"8","author":"Yuan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Al-Abbasi, F.A., Alghamdi, E.A., Baghdadi, M.A., Alamoudi, A.J., El-Halawany, A.M., El-Bassossy, H.M., Aseeri, A.H., and Al-Abd, A.M. (2016). Gingerol Synergizes the Cytotoxic Effects of Doxorubicin against Liver Cancer Cells and Protects from Its Vascular Toxicity. Molecules, 21.","DOI":"10.3390\/molecules21070886"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Mukkavilli, R., Gundala, S.R., Yang, C., Donthamsetty, S., Cantuaria, G., Jadhav, G.R., Vangala, S., Reid, M.D., and Aneja, R. (2014). Modulation of Cytochrome P450 Metabolism and Transport across Intestinal Epithelial Barrier by Ginger Biophenolics. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108386"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Nayak, A.K., Hasnain, M.S., Aminabhavi, T.M., and Torchilin, V.P. (2022). Systems of Nanovesicular Drug Delivery, Academic Press.","DOI":"10.1016\/B978-0-323-91864-0.00026-7"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.copbio.2008.03.003","article-title":"Nutrients and phytochemicals: From bioavailability to bioefficacy beyond antioxidants","volume":"19","author":"Holst","year":"2008","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1159\/000334488","article-title":"Interactions between Herbs and Conventional Drugs: Overview of the Clinical Data","volume":"21","author":"Izzo","year":"2012","journal-title":"Med. Princ. Pract."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"5078","DOI":"10.1038\/s41598-019-41532-3","article-title":"Complementary medicine use during cancer treatment and potential herb-drug interactions from a cross-sectional study in an academic centre","volume":"9","author":"Jermini","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.explore.2010.06.004","article-title":"Evidence-Based Management of Herb-Drug Interaction in Cancer Chemotherapy","volume":"6","author":"Cheng","year":"2010","journal-title":"Explore"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"S88","DOI":"10.1016\/j.jfda.2018.01.003","article-title":"Concurrent administration of anticancer chemotherapy drug and herbal medicine on the perspective of pharmacokinetics","volume":"26","author":"Cheng","year":"2018","journal-title":"J. Food Drug Anal."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1021\/mp300178a","article-title":"Cisplatin-Induced Chemoresistance in Colon Cancer Cells Involves FXR-Dependent and FXR-Independent Up-Regulation of ABC Proteins","volume":"9","author":"Herraez","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"115822","DOI":"10.1016\/j.jep.2022.115822","article-title":"Screening of medicinal plants for possible herb-drug interactions through modulating nuclear receptors, drug-metabolizing enzymes and transporters","volume":"301","author":"Husain","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1007\/s00210-021-02112-3","article-title":"Acquired ABC-transporter overexpression in cancer cells: Transcriptional induction or Darwinian selection?","volume":"394","author":"Theile","year":"2021","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1194\/jlr.M100358-JLR200","article-title":"LXR\/RXR activation enhances basolateral efflux of cholesterol in CaCo-2 cells","volume":"43","author":"Murthy","year":"2002","journal-title":"J. Lipid Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e05357","DOI":"10.1016\/j.heliyon.2020.e05357","article-title":"PXR is a target of (-)-epicatechin in skeletal muscle","volume":"6","author":"Meaney","year":"2020","journal-title":"Heliyon"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/j.jsps.2018.05.016","article-title":"Novel plant inducers of PXR-dependent cytochrome P450 3A4 expression in HepG2 cells","volume":"26","author":"Parvez","year":"2018","journal-title":"Saudi Pharm. J."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s00280-009-1221-4","article-title":"PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line","volume":"66","author":"Harmsen","year":"2010","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.3390\/jcm11061567","article-title":"Herb&ndash;Drug Interaction in Inflammatory Diseases: Review of Phytomedicine and Herbal Supplements","volume":"11","author":"Lippert","year":"2022","journal-title":"J. Clin. Med."},{"key":"ref_138","unstructured":"(2023, March 04). NCT00920803\u2014A Phase 1, Double-Blind, Randomized Clinical Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of SRT501 in Subjects with Colorectal Cancer and Hepatic Metastases, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00920803?term=resveratrol&cond=Colorectal+Cancer&draw=2&rank=2."},{"key":"ref_139","unstructured":"(2023, March 04). NCT00433576\u2014Phase I Repeat-Dose Study of Resveratrol in Colorectal Cancer Patients: Tolerability, Target Tissue Levels and Pharmacodynamics, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00433576?term=resveratrol&cond=Colorectal+Cancer&draw=2&rank=1."},{"key":"ref_140","unstructured":"(2023, March 03). NCT02891538\u2014A Pilot Study to Evaluate the Chemopreventive Effects of Epigallocatechin Gallate (EGCG) in Colorectal Cancer (CRC) Patients With Curative Resections, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02891538."},{"key":"ref_141","unstructured":"(2023, March 03). NCT01239095\u2014Perioperative Administration of Oral Green Tea Extract\/Milk Thistle Extract to Colorectal Cancer Patients Undergoing Colorectal Cancer Resection, a Phase 1 Study, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01239095?term=egcg&cond=Colorectal+Cancer&draw=2&rank=3."},{"key":"ref_142","unstructured":"(2023, March 03). NCT02321969\u2014Green Tea Extracts for the Prevention of Colorectal Adenomas and Colorectal Cancer, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02321969?term=egcg&cond=Colorectal+Cancer&draw=2&rank=2."},{"key":"ref_143","unstructured":"(2023, March 03). NCT00027495\u2014Phase I Pharmacokinetic Trial of Curcuminoids Administered in a Capsule Formulation, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00027495?term=curcumin&cond=Colorectal+Cancer&draw=2&rank=6."},{"key":"ref_144","unstructured":"(2023, March 04). NCT00973869\u2014A Pilot Study of Administration of Curcumin to Determine Colonic Curcumin Tissue Levels in Patients Awaiting Colorectal Endoscopy or Patients With Colorectal Cancer Awaiting Resection, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00973869?term=curcumin&cond=Colorectal+Cancer&draw=2&rank=2."},{"key":"ref_145","unstructured":"(2023, March 05). NCT01344538\u2014Phase II Study of the Effects of Ginger Root Extract on Eicosanoids in Colon Mucosa in People at Normal Risk for Colorectal Cancer, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01344538?term=extract&cond=Colorectal+Cancer&draw=2&rank=2."},{"key":"ref_146","unstructured":"(2023, March 04). NCT01916239\u2014Phase I\u2013II Study of Pomegranate Extract Formulations in Colorectal Cancer Patients: Metabolic and Gene Expression Profiling in Tumoral and Normal Colon Tissues, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01916239?term=extract&cond=Colorectal+Cancer&draw=2&rank=1."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"9125","DOI":"10.2147\/IJN.S259628","article-title":"Phytochemical-Based Nanomedicine for Advanced Cancer Theranostics: Perspectives on Clinical Trials to Clinical Use","volume":"15","author":"Dhupal","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.biotechadv.2016.04.002","article-title":"Nanotechnology for the delivery of phytochemicals in cancer therapy","volume":"34","author":"Xie","year":"2016","journal-title":"Biotechnol. Adv."}],"container-title":["Journal of Xenobiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-4713\/13\/2\/14\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:02:57Z","timestamp":1760122977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-4713\/13\/2\/14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,25]]},"references-count":148,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["jox13020014"],"URL":"https:\/\/doi.org\/10.3390\/jox13020014","relation":{},"ISSN":["2039-4713"],"issn-type":[{"value":"2039-4713","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,25]]}}}