Abstract
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.
Highlights
Considering the growing number of cancer patients and the frequent ineffectiveness of therapies, the priority seems to be searching new and more effective treatments using natural compounds with strong biological activity such as flavonoids—plant compounds that constitute an important element in the human diet [1]
The aim of this study was to assess the influence of apigenin and hesperidin on MCF-7 breast cancer cells treated with doxorubicin, including DNA damage and DNA repair gene expression to better understand observed interactions
MCF-7 on the levelprevious of IC50 preliminary results are shown in Table of of chosen apigenin
Summary
Considering the growing number of cancer patients and the frequent ineffectiveness of therapies, the priority seems to be searching new and more effective treatments using natural compounds with strong biological activity such as flavonoids—plant compounds that constitute an important element in the human diet [1]. There is an increasing number of research studies, proving the antitumor effect of flavonoids is possible owing to their antioxidant properties, and due to other mechanisms connected with the inhibition of cell proliferation, angiogenesis, induction of apoptosis or reduction in protein tyrosine kinases activity [4]. Some flavonoids, depending on the concentration and partial pressure of oxygen in the cells, may have a pro-oxidative effect and in this way kill cancer cells [5]. In addition to their cytotoxic properties to cancer cells, many studies have shown that these compounds enhance the effects of standard chemotherapeutics [6,7,8]
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