Please use this identifier to cite or link to this item: https://scidar.kg.ac.rs/handle/123456789/22360
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dc.contributor.authorĆurčić Milutinović, Milena-
dc.contributor.authorRistanović, Filip-
dc.contributor.authorRadenkovic, Nikola-
dc.contributor.authorCvetkovic, Danijela-
dc.contributor.authorRadenković, Sandra-
dc.contributor.authorStankovic, Milan-
dc.contributor.authorNikodijević, Danijela-
dc.date.accessioned2025-06-05T10:02:36Z-
dc.date.available2025-06-05T10:02:36Z-
dc.date.issued2025-
dc.identifier.issn1424-8247en_US
dc.identifier.urihttps://scidar.kg.ac.rs/handle/123456789/22360-
dc.description.abstractBackground/Objectives: Multidrug resistance is one the leading problems in cancer treatment, where the overexpression of P-gp and other drug efflux pumps is regarded as the primary cause. With the intention to develop transporter inhibitors, natural products such as phenolics have shown great potential and diverse attention recently. Among these, isorhamnetin (ISO), an O-methylated flavonol, is predominantly found in the fruits and leaves of various plants. Thus, this study aimed to investigate the effects of ISO on the mRNA expression of membrane transporters P-gp, BCRP, MRP 1, 2, and 5, the protein expression of P-gp, as well as the GSTP1 and GSH content in DLD1 and HCT-116 colon cancer cells. Methods: The cytotoxic effect of isorhamnetin is assessed using an MTT test, while qPCR and immunocytochemistry methods were used to determine gene and protein expression levels. The concentration of reduced glutathione was determined using the colorimetric method. Results: Based on the results, ISO can modulate the expression of transporters responsible for the resistance development (all transporters on the transcriptional level were downregulated in DLD1 cells, while only MRP1 on HCT-116 cells, and reduced P-gp protein expression on both investigated cell lines). Increased glutathione content in treated cells and GSTP1 expression suggest metabolizing the ISO and potential ejection with GSH-dependent pumps. Conclusions: Thus, in future experiments, ISO as a natural medicinal compound could be used as a chemosensitizer to prevent or overcome membrane transporter-mediated drug resistance.en_US
dc.language.isoenen_US
dc.relation.ispartofPharmaceuticals (Basel, Switzerland)en_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subjectBCRPen_US
dc.subjectisorhamnetinen_US
dc.subjectcancer cell resistanceen_US
dc.subjectMDRen_US
dc.subjectMRPsen_US
dc.subjectP-gpen_US
dc.titleModulation of the Main Resistance-Associated ABC Transporter's Expression by Plant Flavonol Isorhamnetinen_US
dc.typearticleen_US
dc.description.versionPublisheden_US
dc.identifier.doi10.3390/ph18040494en_US
dc.type.versionPublishedVersionen_US
Appears in Collections:Faculty of Science, Kragujevac

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