Antiproliferative Effects of Hop-derived Prenylflavonoids and Their Influence on the Efficacy of Oxaliplatine, 5-fluorouracil and Irinotecan in Human ColorectalC Cells

Abstract

Beer, the most popular beverage containing hops, is also frequently consumed by cancer patients. Moreover, non-alcoholic beer, owing to its nutritional value and high content of biological active compounds, is sometimes recommended to patients by oncologists. However, the potential benefits and negatives have to date not been sufficiently evaluated. The present study was designed to examine the effects of four main hop-derived prenylflavonoids on the viability, reactive oxygen species (ROS) formation, activity of caspases, and efficiency of the chemotherapeutics 5-fluorouracil (5-FU), oxaliplatin (OxPt) and irinotecan (IRI) in colorectal cancer cell lines SW480, SW620 and CaCo-2. All the prenylflavonoids exerted substantial antiproliferative effects in all cell lines, with xanthohumol being the most effective (IC₅₀ ranging from 3.6 to 7.3 µM). Isoxanthohumol increased ROS formation and the activity of caspases-3/7, but 6-prenylnaringenin and 8-prenylnaringenin exerted antioxidant properties. As 6-prenylnaringenin acted synergistically with IRI, its potential in combination therapy deserves further study. However, other prenylflavonoids acted antagonistically with all chemotherapeutics at least in one cell line. Therefore, consumption of beer during chemotherapy with 5-FU, OxPt and IRI should be avoided, as the prenylflavonoids in beer could decrease the efficacy of the treatment.

Keywords: 5-fluorouracil; caspase activity; colorectal carcinoma cells; irinotecan; isoxanthohumol; naringenin; oxaliplatin; prenylflavonoids.

Figure 1

Chemical structures of the studied prenylflavonoids and naringenin.

Figure 2

Effect of prenylflavonoids on the viability of SW480 (a), SW620 (b), proliferating CaCo-2 (c), and differentiated CaCo-2 cells (d) after 72 h of treatment. The cell viability was assayed using the neutral red uptake assay. Data are presented as a percentage of the respective control (= 100%) and represent the mean ± S.D. (n = 3) (• data with p < 0.01, * p < 0.001, one-way ANOVA with Dunett’s test).

Figure 3

Effect of prenylflavonoids and naringenin on the ROS formation in SW620 cells. Data represent the mean ± S.D. (n = 3) (* data with p < 0.001, one-way ANOVA with Dunett’s test).

Figure 4

Effect of prenylflavonoids and naringenin on the activation of apoptosis in SW620 cells. The activity of caspases-3/7 was assessed after 4-, 8-, and 24-hour incubation. Data presented as percentage of untreated control (= 100%), represent the mean ± S.D. (n = 3) (* data with p < 0.05, ** p < 0.001, one-way ANOVA with Dunett’s test).

Figure 5

Effect of flavonoid–cytostatic combinations on the activation of apoptosis in SW620 cells. The activity of caspases 3/7 was assessed after 8-hour incubation (a) and 24-hour incubation (b). Data are presented as a percentage of respective cytostatic-treated control (= 100%) and represent the mean ± S.D. (n = 3) (* data with p < 0.05, ** p < 0.01, *** p < 0.001, one-way ANOVA with Dunett’s test).