Pichler Christoph, Ferk Franziska, Al-Serori Halh, Huber Wolfgang, Jäger Walter, Waldherr Monika, Mišík Miroslav, Kundi Michael, Nersesyan Armen, Herbacek Irene, Knasmueller Siegfried
Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
Department for Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Vienna, Austria.
Cancer Prev Res (Phila). 2017 Feb;10(2):153-160. doi: 10.1158/1940-6207.CAPR-15-0378. Epub 2016 Dec 6.
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.
黄腐酚（XN）是一种存在于啤酒和软饮料中的啤酒花类黄酮。体外和动物研究表明，XN具有保护DNA和抗癌特性。为了确定它是否对人类有DNA保护作用，开展了一项干预试验，参与者（n = 22）饮用含XN的饮料（12毫克XN/人/天）。我们监测了主要膳食致癌物（即亚硝基二甲胺（NDMA）、苯并[a]芘（B[a]P）和杂环芳香胺2-氨基-3-甲基咪唑[4,5-f]喹啉（IQ））代表物诱导的DNA损伤的预防情况。在干预前、干预期间和干预后收集淋巴细胞，并与致癌物和人肝匀浆（S9）一起孵育。我们发现饮用该饮料后，B[a]P和IQ诱导的DNA损伤大幅减少（两种物质的P均<0.001）；此外，对于亚硝胺也发现了适度但显著的保护作用。一项针对XN药丸的后续试验（n = 10）结果表明，这些作用是由该类黄酮引起的，并在γH2AX实验中得到证实。为了阐明潜在机制，我们测量了谷胱甘肽相关解毒的几个参数。我们发现α-谷胱甘肽S-转移酶（α-GST）明显诱导（增加42.8%，P < 0.05），但π-谷胱甘肽S-转移酶（π-GST）没有变化。这一观察结果为DNA保护作用提供了部分解释，并表明该类黄酮还能抵御其他由α-GST解毒的致癌物。综上所述，我们的研究结果支持XN在人类中具有抗癌特性这一假设。《癌症预防研究》；10(2)；153 - 60。©2016美国癌症研究协会。
