American Journal of Clinical Nutrition, 2014, 100(Supplement_1):431S-6S.

Genistein inhibits human prostate cancer cell detachment, invasion, and metastasis

Janet M Pavese, Sankar N Krishna, Raymond C Bergan

From the Department of Medicine (JMP, SNK, and RCB), the Robert H Lurie Cancer Center (RCB), and the Center for Molecular Innovation and Drug Discovery (RCB), Northwestern University, Chicago, IL

Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the United States and the second leading cause of cancer death. Death is not caused by the primary tumor but rather by the formation of distinct metastatic tumors. Therefore, prevention of metastasis is of utmost importance. The natural product genistein, found in high amounts in soy products, has been implicated in preventing PCa formation and metastasis in men who consume high amounts of soy. In vitro studies and in vivo rodent models that used human PCa cells, as well as prospective human clinical trials, provide a mechanistic explanation directly supporting genistein as an antimetastatic agent. Specifically, our group showed that genistein inhibits cell detachment, protease production, cell invasion, and human PCa metastasis at concentrations achieved in humans with dietary intake. Finally, phase I and phase II clinical trials conducted by us and others showed that concentrations of genistein associated with antimetastatic efficacy in preclinical models are achievable in humans, and treatment with genistein inhibits pathways that regulate metastatic transformation in human prostate tissue.

美国《美国临床营养学杂志》，2014年7月

金雀异黄素抑制人体前列腺癌细胞的脱离、 侵袭及转移

珍妮特 M帕韦泽；桑卡N克里希纳；雷蒙德C 贝尔加

美国芝加哥西北大学罗伯特 H 卢瑞癌症中心 (RCB) 和分子创新与药物发现中心(RCB)医学系 （就业选配计划，SNK 及 RCB）

在美国前列腺癌 (PCa) 在男性中是最常见的癌症，并且是癌症死亡的第二个主要原因。死亡不是由于原发性肿瘤，而是由不同的转移性肿瘤造成的。因此，预防转移至关重要。天然物质金雀异黄素，在豆制品中被大量发现，与大量食用大豆男性的预防 PCa 形成和转移有关。使用人体PCa细胞的体外和体内的啮齿动物模型，以及前瞻性的人体临床试验，提供了能直接支持金雀异黄素作为抗癌细胞扩散和转移的解释。特别地，我们的团队发现，金雀异黄素抑制细胞分离、 蛋白酶生产、 细胞侵袭以及在浓度达到人体膳食摄入量的患者的 PCa 转移。最后，我们和其他人进行的 I期和II 期临床试验表明，金雀异黄素的浓度与临床前的模型抗转移的疗效相关联，并且用金雀异黄素治疗抑制调节人体前列腺组织转移转型的通路。