Cancer chemopreventive activity of Xanthohumol, a natural product derived from hop.
Cancer chemopreventive activity of Xanthohumol, a natural product derived from hop.
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发表时间：
2002-09
影响因子：
5.7
通讯作者：
C. Gerhauser;A. Alt;E. Heiss;A. Gamal-Eldeen;K. Klimo;J. Knauft;I. Neumann;H. Scherf;N. Frank;H. Bartsch;H. Becker
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作者：
C. Gerhauser;A. Alt;E. Heiss;A. Gamal-Eldeen;K. Klimo;J. Knauft;I. Neumann;H. Scherf;N. Frank;H. Bartsch;H. Becker
有效的癌症化学预防剂的表征和使用已成为公共卫生相关研究中的重要问题。为了确定新的潜在的化学预防剂，我们已经建立了一个相互关联的一系列生物测定系统，靶向分子机制相关的预防肿瘤的发展。本文报道了啤酒花（Humulus Iupulus L.）在癌发生的起始、促进和进展阶段具有异常广谱的抑制机制。与抗引发潜力一致，XN有效地调节参与致癌物代谢和解毒的酶的活性。此外，XN能够清除活性氧，包括羟基自由基和过氧自由基，并抑制超氧阴离子自由基和一氧化氮的产生。作为潜在的抗肿瘤促进机制，它通过抑制环氧合酶-1和环氧合酶-2活性显示出抗炎特性，并且是抗雌激素的，但不具有内在的雌激素潜力。XN的抗增殖机制包括抑制DNA合成和诱导细胞周期停滞在S期、凋亡和细胞分化。重要的是，纳摩尔浓度的XN可防止小鼠乳腺器官培养中致癌物诱导的癌前病变。由于XN很容易环化为黄烷酮异黄腐酚，因此在整个研究中比较了两种化合物的活性。总之，我们的数据为XN作为一种新型的、现成的化学预防剂的潜在应用提供了证据，一旦在动物模型中建立了有效性和安全性，就有必要进行临床研究。
Characterization and use of effective cancer chemopreventive agents have become important issues in public health-related research. Aiming to identify novel potential chemopreventive agents, we have established an interrelated series of bioassay systems targeting molecular mechanisms relevant for the prevention of tumor development. We report anticarcinogenic properties of Xanthohumol (XN), a prenylated chalcone from hop (Humulus Iupulus L.) with an exceptional broad spectrum of inhibitory mechanisms at the initiation, promotion, and progression stage of carcinogenesis. Consistent with anti-initiating potential, XN potently modulates the activity of enzymes involved in carcinogen metabolism and detoxification. Moreover, XN is able to scavenge reactive oxygen species, including hydroxyl- and peroxyl radicals, and to inhibit superoxide anion radical and nitric oxide production. As potential antitumor-promoting mechanisms, it demonstrates anti-inflammatory properties by inhibition of cyclooxygenase-1 and cyclooxygenase-2 activity and is antiestrogenic without possessing intrinsic estrogenic potential. Antiproliferative mechanisms of XN to prevent carcinogenesis in the progression phase include inhibition of DNA synthesis and induction of cell cycle arrest in S phase, apoptosis, and cell differentiation. Importantly, XN at nanomolar concentrations prevents carcinogen-induced preneoplastic lesions in mouse mammary gland organ culture. Because XN is easily cyclized to the flavanone isoxanthohumol, activities of both compounds were compared throughout the study. Together, our data provide evidence for the potential application of XN as a novel, readily available chemopreventive agent, and clinical investigations are warranted once efficacy and safety in animal models have been established.