Please use this identifier to cite or link to this item: https://scidar.kg.ac.rs/handle/123456789/22360
Title: Modulation of the Main Resistance-Associated ABC Transporter's Expression by Plant Flavonol Isorhamnetin
Authors: Ćurčić Milutinović, Milena
Ristanović, Filip
Radenkovic, Nikola
Cvetkovic, Danijela
Radenković, Sandra
Stankovic, Milan
Nikodijević, Danijela
Journal: Pharmaceuticals (Basel, Switzerland)
Issue Date: 2025
Abstract: Background/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.
URI: https://scidar.kg.ac.rs/handle/123456789/22360
Type: article
DOI: 10.3390/ph18040494
ISSN: 1424-8247
Appears in Collections:Faculty of Science, Kragujevac

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