Abstract
Xanthohumol (XN), a prenylated flavonoid found in hops, inhibits growth in a variety of cancer cell lines; however, its use raises concerns as gut microbiota and the host’s hepatic cytochrome P450 enzymes metabolize it into the most potent phytoestrogen known, 8-prenylnaringenin (8-PN). The XN derivatives dihydroxanthohumol (DXN) and tetrahydroxanthohumol (TXN) are not metabolized into 8-PN and they show higher tissue concentrations in vivo compared with XN when orally administered to mice at the same dose. Here we show that DXN and TXN possess improved anti-proliferative activity compared with XN in two colon (HCT116, HT29) and two hepatocellular (HepG2, Huh7) carcinoma cell lines, as indicated by their respective IC50 values. Furthermore, XN, DXN, and TXN induce extensive apoptosis in all these carcinoma cell lines. Finally, TXN induces G0/G1 cell cycle arrest in the colon carcinoma cell line HT29. Our findings suggest that DXN and TXN could show promise as therapeutic agents against colorectal and liver cancer in preclinical studies without the drawback of metabolism into a phytoestrogen.
Highlights
First discovered at the turn of the twentieth century by Power et al, XN is a simple prenylated flavonoid found in the female inflorescences, or hop cones, of the hop plant Humulus lupulus [1]
While XN and DXN do not appear to induce cell cycle arrest, HT29 cells treated with TXN arrest in the G0/G1 phase of the cell cycle
These findings demonstrate that the two non-estrogenic XN derivatives are attractive alternatives to test along with XN in future preclinical studies using mouse models of colorectal and hepatocellular carcinoma
Summary
First discovered at the turn of the twentieth century by Power et al, XN is a simple prenylated flavonoid found in the female inflorescences, or hop cones, of the hop plant Humulus lupulus [1]. Extensive studies show XN inhibits cancer cell growth in vitro, and reduces weight gain and improves cognitive function in vivo [2,3,4,5,6,7,8,9] Despite these positive effects, the use of XN raises concerns, as it was shown both in vitro and in vivo that XN is metabolized into 8-prenylnaringenin (8-PN), the most potent phytoestrogen currently known [10]. While XN and DXN do not appear to induce cell cycle arrest, HT29 cells treated with TXN arrest in the G0/G1 phase of the cell cycle These findings demonstrate that the two non-estrogenic XN derivatives are attractive alternatives to test along with XN in future preclinical studies using mouse models of colorectal and hepatocellular carcinoma. FXigNuorer aTdXaNp.teFdigfurorema[d3a].pted from [3]
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