Abstract
Cancer is commonly diagnosed in dogs over the age of 10 and is a leading cause of death due to the lack of effective drugs. Flavonoids possess antioxidant, anti-inflammatory and anticarcinogenic properties and have been studied as chemopreventive agents in human cancer therapy. However, the literature on dogs is sparse. In this study, we analyzed the effect of nine flavonoids on cell viability, DNA damage and topoisomerase IIa/IIb gene expression in a canine tumor cell line (DH82). Apigenin, luteolin, trans-chalcone and 4-methoxychalcone showed the highest degree of cytotoxicity in the absence of considerable DNA damage, whereas genistein exhibited low cytotoxicity but induced a high level of DNA damage. These five flavonoids inhibited topoisomerase IIa and IIb gene expression to variable extents and with variable specificity. Genistein exerted a lower inhibitory effect on the two topoisomerases than luteolin and apigenin. trans-Chalcone and 4-methoxychalcone exerted greater inhibition of topoisomerase IIa expression than topoisomerase IIb. The differences in the effects between genistein and luteolin and apigenin might be explained by the position of ring B, whereas the more specific effect of chalcones on topoisomerase IIa might be due to their open chain structure.
Highlights
Dogs have accompanied their owners in the increase in life expectancy as a result of advances in veterinary practice, pet food and veterinary medicine
Studies have shown that flavonoids exert cytotoxic activity against cancer cells, a property that can be explored for the development of new cancer therapies [32]
In an attempt to extend these therapies to dogs, we evaluated the cytotoxic effects of flavonoids in the canine malignant histiocytosis cell line
Summary
Dogs have accompanied their owners in the increase in life expectancy as a result of advances in veterinary practice, pet food and veterinary medicine. Despite advances in oncology that have permitted successful treatment, cancer continues to be a leading cause of death in humans and animals In this respect, alternative approaches are needed to change this scenario and the use of dietary flavonoids as chemopreventive and chemotherapeutic agents is gaining attention for human cancers, but is still overlooked for dogs [1,4]. In the presence of metals such as copper and iron, flavonoids increase the formation of free radicals and act as pro-oxidants, causing DNA oxidation, with consequent genotoxic and mutagenic effects including DNA double-strand breaks [26] This property can be exploited against tumor cells since these cells contain a higher concentration of intracellular copper, especially bound to DNA, increasing the genotoxic effect of flavonoids [27]. Different letters indicate statistically significant results (p < 0.05)
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