Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity

Molecules

Marta Wojcik¹  Aleksandra Jozefczyk²  Jaroslaw Dudka³  Magdalena Iwan³  Marta Ostrowska-Lesko³  Grzegorz Adamczuk⁴  Agnieszka Korga-Plewko⁴  Ewelina Humeniuk⁴  Monika Michalczyk⁴ 

[1] Department of Pathophysiology, University of Life Sciences, 12 Akademicka Street, 20-033 Lublin, Poland;Department of Pharmacognosy with Medicinal Plant Laboratory, Medical University of Lublin, 1 Chodzko Street, 20-090 Lublin, Poland;Department of Toxicology, Medical University of Lublin, 6 Chodzko Street, 20-093 Lublin, Poland;Independent Medical Biology Unit, Medical University of Lublin, 8b Jaczewski Street, 20-090 Lublin, Poland;

关键词: apigenin;    doxorubicin;    hesperidin;    DNA repair;    DNA damage;    oxidative stress;   

DOI  :  10.3390/molecules25194421

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown