Abstract
Prenylflavonoids in the human organism exhibit various health-beneficial activities, although they may interfere with drugs via the modulation of the expression and/or activity of drug-metabolizing enzymes. As intestinal cells are exposed to the highest concentrations of prenylflavonoids, we decided to study the cytotoxicity and modulatory effects of the four main hop-derived prenylflavonoids on the activities and mRNA expression of the main drug-conjugating enzymes in human CaCo-2 cells. Proliferating CaCo-2 cells were used for these purposes as a model of colorectal cancer cells, and differentiated CaCo-2 cells were used as an enterocyte-like model. All the tested prenylflavonoids inhibited the CaCo-2 cells proliferation, with xanthohumol proving the most effective (IC50 8.5 µM). The prenylflavonoids modulated the activities and expressions of the studied enzymes to a greater extent in the differentiated, as opposed to the proliferating, CaCo-2 cells. In the differentiated cells, all the prenylflavonoids caused a marked increase in glutathione S-transferase and catechol-O-methyltransferase activities, while the activity of sulfotransferase was significantly inhibited. Moreover, the prenylflavonoids upregulated the mRNA expression of uridine diphosphate (UDP)-glucuronosyl transferase 1A6 and downregulated that of glutathione S-transferase 1A1/2.
Highlights
Dietary factors may play a crucial role in the prevention and progression of various lifestyle diseases, such as diabetes mellitus, cancer, obesity and cardiovascular diseases
All prenylflavonoids were dissolved in dimethyl sulfoxide (DMSO) and their stock solutions were stored at 4 ◦ C in the dark
This study was focused on the evaluation of the effect of four commonly occurring prenylflavonoids, namely xanthohumol (XH), isoxanthohumol (IXH), 6-prenylnaringenin (6-PN) and 8-prenylnaringenin
Summary
Dietary factors may play a crucial role in the prevention and progression of various lifestyle diseases, such as diabetes mellitus, cancer, obesity and cardiovascular diseases. An increased dietary intake of antioxidants such as polyphenols, vitamins (C, E) and carotenoids may be an important factor in the prevention of lifestyle diseases. Flavonoids, which represent approximately two-thirds of all dietary polyphenols, possess multiple biological and pharmacological activities (e.g., antioxidant, anti-inflammatory, anti-cancer activities) [2]. The prenylated flavonoids, XH, IXH, 6-PN and 8-PN, showed stronger cytotoxic effects in human colorectal cancer cell lines than did the parent compound naringenin [8]. Multiple biological targets of prenylflavonoids, such as aromatase, the aryl hydrocarbon receptor, nuclear factor NF-κB and the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid-2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway, have been identified and reviewed in [4]
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