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Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity
A number of studies have confirmed anti-tumor activity of flavonoids and their ability to enhance the effectiveness of classical anticancer drugs. The mechanism of this phenomenon is difficult to explain because of the ambivalent nature of these compounds. Many therapeutic properties of these compou...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582946/ https://www.ncbi.nlm.nih.gov/pubmed/32993087 http://dx.doi.org/10.3390/molecules25194421 |
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author | Korga-Plewko, Agnieszka Michalczyk, Monika Adamczuk, Grzegorz Humeniuk, Ewelina Ostrowska-Lesko, Marta Jozefczyk, Aleksandra Iwan, Magdalena Wojcik, Marta Dudka, Jaroslaw |
author_facet | Korga-Plewko, Agnieszka Michalczyk, Monika Adamczuk, Grzegorz Humeniuk, Ewelina Ostrowska-Lesko, Marta Jozefczyk, Aleksandra Iwan, Magdalena Wojcik, Marta Dudka, Jaroslaw |
author_sort | Korga-Plewko, Agnieszka |
collection | PubMed |
description | A number of studies have confirmed anti-tumor activity of flavonoids and their ability to enhance the effectiveness of classical anticancer drugs. The mechanism of this phenomenon is difficult to explain because of the ambivalent nature of these compounds. Many therapeutic properties of these compounds are attributed to their antioxidant activity; however, it is known that they can act as oxidants. The aim of this study was to assess the influence of apigenin and hesperidin on MCF-7 breast cancer cells with doxorubicin. The cytotoxic effect was determined using an MTT test and cell cycle analysis. To evaluate the possible interaction mechanism, reduced glutathione levels, as well as the DNA oxidative damage and the double strand breaks, were evaluated. Additionally, mRNA expression of genes related to DNA repair was assessed. It was demonstrated that flavonoids intensified the cytotoxic effect of doxorubicin despite flavonoids reduced oxidative damage caused by the drug. At the same time, the number of double strand breaks significantly increased and expression of tested genes was downregulated. In conclusion, both apigenin and hesperidin enhance the cytotoxic effects of doxorubicin on breast cancer cells, and this phenomenon occurs regardless of oxidative stress but is accompanied by disorders of DNA damage response mechanisms. |
format | Online Article Text |
id | pubmed-7582946 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75829462020-10-28 Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity Korga-Plewko, Agnieszka Michalczyk, Monika Adamczuk, Grzegorz Humeniuk, Ewelina Ostrowska-Lesko, Marta Jozefczyk, Aleksandra Iwan, Magdalena Wojcik, Marta Dudka, Jaroslaw Molecules Article A number of studies have confirmed anti-tumor activity of flavonoids and their ability to enhance the effectiveness of classical anticancer drugs. The mechanism of this phenomenon is difficult to explain because of the ambivalent nature of these compounds. Many therapeutic properties of these compounds are attributed to their antioxidant activity; however, it is known that they can act as oxidants. The aim of this study was to assess the influence of apigenin and hesperidin on MCF-7 breast cancer cells with doxorubicin. The cytotoxic effect was determined using an MTT test and cell cycle analysis. To evaluate the possible interaction mechanism, reduced glutathione levels, as well as the DNA oxidative damage and the double strand breaks, were evaluated. Additionally, mRNA expression of genes related to DNA repair was assessed. It was demonstrated that flavonoids intensified the cytotoxic effect of doxorubicin despite flavonoids reduced oxidative damage caused by the drug. At the same time, the number of double strand breaks significantly increased and expression of tested genes was downregulated. In conclusion, both apigenin and hesperidin enhance the cytotoxic effects of doxorubicin on breast cancer cells, and this phenomenon occurs regardless of oxidative stress but is accompanied by disorders of DNA damage response mechanisms. MDPI 2020-09-26 /pmc/articles/PMC7582946/ /pubmed/32993087 http://dx.doi.org/10.3390/molecules25194421 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Korga-Plewko, Agnieszka Michalczyk, Monika Adamczuk, Grzegorz Humeniuk, Ewelina Ostrowska-Lesko, Marta Jozefczyk, Aleksandra Iwan, Magdalena Wojcik, Marta Dudka, Jaroslaw Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity |
title | Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity |
title_full | Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity |
title_fullStr | Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity |
title_full_unstemmed | Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity |
title_short | Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity |
title_sort | apigenin and hesperidin downregulate dna repair genes in mcf-7 breast cancer cells and augment doxorubicin toxicity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582946/ https://www.ncbi.nlm.nih.gov/pubmed/32993087 http://dx.doi.org/10.3390/molecules25194421 |
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