Xanthohumol Prevents DNA Damage by Dietary Carcinogens: Results of a Human Intervention Trial

Abstract

Xanthohumol (XN) is a hop flavonoid contained in beers and soft drinks. In vitro and animal studies indicated that XN has DNA and cancer protective properties. To find out if it causes DNA protective effects in humans, an intervention trial was conducted in which the participants (n = 22) consumed a XN containing drink (12 mg XN/P/d). We monitored prevention of DNA damage induced by representatives of major groups of dietary carcinogens [i.e., nitrosodimethylamine (NDMA) benzo(a)pyrene (B(a)P) and the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)]. Lymphocytes were collected before, during, and after the intervention and incubated with the carcinogens and with human liver homogenate (S9). We found substantial reduction of B(a)P and IQ (P < 0.001 for both substances) induced DNA damage after consumption of the beverage; also, with the nitrosamine a moderate, but significant protective effect was found. The results of a follow-up trial (n = 10) with XN pills showed that the effects are caused by the flavonoid and were confirmed in γH2AX experiments. To elucidate the underlying mechanisms we measured several parameters of glutathione related detoxification. We found clear induction of α-GST (by 42.8%, P < 0.05), but no alteration of π-GST. This observation provides a partial explanation for the DNA protective effects and indicates that the flavonoid also protects against other carcinogens that are detoxified by α-GST. Taken together, our findings support the assumption that XN has anticarcinogenic properties in humans. Cancer Prev Res; 10(2); 153-60. ©2016 AACR.

Xanthohumol, a Prenylated Flavonoid from Hops, Induces DNA Damages in Colorectal Cancer Cells and Sensitizes SW480 Cells to the SN38 Chemotherapeutic Agent

“…These properties have made it possible to classify this chalcone in the category of chemopreventive molecules. Moreover, a number of studies have been able to show the ability of Xn to prevent DNA damage induced by numerous cytotoxic agents [56][57][58]. This study highlights for the first time the ability of Xn to sensitize colon cancer cells to an anticancer agent such as SN38.…”

Genoprotective activities of plant natural substances in cancer and chemopreventive strategies in the context of 3P medicine

“…Consumption of diet rich in substances of plant origin, such as cruciferous vegetable, kiwifruits, fruit juice, or diet of Mediterranean pattern, as well as beverages including tea or coffee, is associated with potent cancer preventive properties. The importance of genoprotective abilities of plant substances was evaluated in clinical, mainly preventive studies conducted on healthy or high-risk individuals [18,24,26,[149][150][151][152][153][154][155][156][157][158]. Antioxidant properties of phytochemicals A mixed berry juice rich in anthocyanin/polyphenolics decreased oxidative DNA damage and increased level of reduced glutathione (GSH) and glutathione status in cells of healthy participants while the observed decrease in oxidative DNA damage may be associated with direct antioxidant effects such as ROS scavenging or chelation [150].…”

The role of nutrition in influencing mechanisms involved in environmentally mediated diseases

“…These naturally occurring compounds, which include xanthohumol, exhibit antioxidant and anti-inflammatory properties, and can modulate the metabolism of carcinogens by inhibition of distinct phase 1 metabolic enzymes and activation of phase 2 detoxifying enzymes (26). In a recent human study it was found that xanthohumol can prevent DNA damage by dietary carcinogens, such as 2-amino-3-methylimidazo[4,5-f]quinolone (27), which can be formed during the cooking of meat and fish (28). Also, xanthohumol can have anti-inflammatory actions in cancer cells by suppressing prostaglandin E2 production and cell migration (29).…”