Enhancement of doxorubicin efficacy by diosmetin through DNA damage accumulation and P-glycoprotein inhibition in breast cancer cells
Abstract Doxorubicin (DOX) is widely used in treatment; however, its efficacy is often compromised by multidrug resistance (MDR), limiting therapeutic outcomes. This study investigates the anticancer potential of diosmetin (DT), a metabolite of diosmin commonly used in chronic venous insufficiency,...
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-16681-3 |
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| author | Monika Michalczyk Ewelina Humeniuk Joanna Kubik Grzegorz Adamczuk Mariola Michalczuk Barbara Madej-Czerwonka Maciej Czerwonka Agnieszka Korga-Plewko |
| author_facet | Monika Michalczyk Ewelina Humeniuk Joanna Kubik Grzegorz Adamczuk Mariola Michalczuk Barbara Madej-Czerwonka Maciej Czerwonka Agnieszka Korga-Plewko |
| author_sort | Monika Michalczyk |
| collection | DOAJ |
| description | Abstract Doxorubicin (DOX) is widely used in treatment; however, its efficacy is often compromised by multidrug resistance (MDR), limiting therapeutic outcomes. This study investigates the anticancer potential of diosmetin (DT), a metabolite of diosmin commonly used in chronic venous insufficiency, and its ability to enhance the efficacy of DOX in the treatment of breast cancer. Several breast cancer cell lines were used to assess the effects of DT and DOX on cell viability. The MCF-7 cell line, which showed the most significant effect, was selected for further investigation. The effects of DT on apoptosis, DNA damage, and P-glycoprotein expression and activity were analyzed. DT significantly enhanced DOX-induced apoptosis and DNA damage, while downregulating ABCB1 expression and activity, a key factor in MDR development. These findings highlight the potential of DT as a valuable adjuvant in breast cancer therapy by enhancing the efficacy of DOX. Its ability to overcome multidrug resistance mechanisms underlines its potential for future clinical trials aimed at developing effective treatments. |
| format | Article |
| id | doaj-art-c6f0ae0588f247c3b43bbe01db804700 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-c6f0ae0588f247c3b43bbe01db8047002025-08-24T11:21:37ZengNature PortfolioScientific Reports2045-23222025-08-0115111510.1038/s41598-025-16681-3Enhancement of doxorubicin efficacy by diosmetin through DNA damage accumulation and P-glycoprotein inhibition in breast cancer cellsMonika Michalczyk0Ewelina Humeniuk1Joanna Kubik2Grzegorz Adamczuk3Mariola Michalczuk4Barbara Madej-Czerwonka5Maciej Czerwonka6Agnieszka Korga-Plewko7Independent Medical Biology Unit, Medical University of LublinIndependent Medical Biology Unit, Medical University of LublinIndependent Medical Biology Unit, Medical University of LublinIndependent Medical Biology Unit, Medical University of LublinIndependent Medical Biology Unit, Medical University of LublinHuman Anatomy Department, Faculty of Medicine, Medical University of LublinFirst Department of Surgery, Jagiellonian University Medical CollegeIndependent Medical Biology Unit, Medical University of LublinAbstract Doxorubicin (DOX) is widely used in treatment; however, its efficacy is often compromised by multidrug resistance (MDR), limiting therapeutic outcomes. This study investigates the anticancer potential of diosmetin (DT), a metabolite of diosmin commonly used in chronic venous insufficiency, and its ability to enhance the efficacy of DOX in the treatment of breast cancer. Several breast cancer cell lines were used to assess the effects of DT and DOX on cell viability. The MCF-7 cell line, which showed the most significant effect, was selected for further investigation. The effects of DT on apoptosis, DNA damage, and P-glycoprotein expression and activity were analyzed. DT significantly enhanced DOX-induced apoptosis and DNA damage, while downregulating ABCB1 expression and activity, a key factor in MDR development. These findings highlight the potential of DT as a valuable adjuvant in breast cancer therapy by enhancing the efficacy of DOX. Its ability to overcome multidrug resistance mechanisms underlines its potential for future clinical trials aimed at developing effective treatments.https://doi.org/10.1038/s41598-025-16681-3DiosmetinDiosminDoxorubicinDNA damageABCB1 activity |
| spellingShingle | Monika Michalczyk Ewelina Humeniuk Joanna Kubik Grzegorz Adamczuk Mariola Michalczuk Barbara Madej-Czerwonka Maciej Czerwonka Agnieszka Korga-Plewko Enhancement of doxorubicin efficacy by diosmetin through DNA damage accumulation and P-glycoprotein inhibition in breast cancer cells Scientific Reports Diosmetin Diosmin Doxorubicin DNA damage ABCB1 activity |
| title | Enhancement of doxorubicin efficacy by diosmetin through DNA damage accumulation and P-glycoprotein inhibition in breast cancer cells |
| title_full | Enhancement of doxorubicin efficacy by diosmetin through DNA damage accumulation and P-glycoprotein inhibition in breast cancer cells |
| title_fullStr | Enhancement of doxorubicin efficacy by diosmetin through DNA damage accumulation and P-glycoprotein inhibition in breast cancer cells |
| title_full_unstemmed | Enhancement of doxorubicin efficacy by diosmetin through DNA damage accumulation and P-glycoprotein inhibition in breast cancer cells |
| title_short | Enhancement of doxorubicin efficacy by diosmetin through DNA damage accumulation and P-glycoprotein inhibition in breast cancer cells |
| title_sort | enhancement of doxorubicin efficacy by diosmetin through dna damage accumulation and p glycoprotein inhibition in breast cancer cells |
| topic | Diosmetin Diosmin Doxorubicin DNA damage ABCB1 activity |
| url | https://doi.org/10.1038/s41598-025-16681-3 |
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