Journal of Nutrition, 1995, 125(3 Suppl):784S.

Evaluation of the biochemical targets of genistein in tumor cells

Greg Peterson

Department of Biochemistry, University of Alabama at Birmingham 35294

Although data from epidemiological studies and cancer models suggest that genistein plays an important role in cancer prevention, the biochemical target(s) of genistein action is (are) not known. Genistein is a potent in vitro inhibitor of protein tyrosine kinase (PTK) activity, especially that of the epidermal growth factor receptor (EGF-R), having little effect on serine/threonine kinases. This led to the suggestion that genistein might exert its anti-cancer effects through inhibiting the activity of EGF-R PTK, or other crucial PTK's in vivo. Subsequent studies on intact tumor cell lines demonstrated that EGF-R and other growth factor receptors are able to transmit mitogenic signals in the presence of genistein. In fact, it is difficult to detect decreases in the tyrosine phosphorylation of discrete proteins after genistein treatment. Other mechanisms for the effect of genistein have been suggested from in vitro and cell culture data. Genistein not only inhibits the activity of purified topoisomerase II in vitro, but also leads to the accumulation of protein-associated single strand breaks in whole cells. Genistein also inhibits the production of reactive oxygen species which may lead to tissue damage and DNA modification. Additionally, genistein acts as a weak estrogen, modifies cellular differentiation programs, inhibits angiogenesis. modulates cell cycle events and may precipitate apoptosis. However, few of the above mechanisms in tumor cells are sensitive to the physiological serum concentrations of genistein (< 18.5 mumol/L, or < 5 micrograms/mL). Primary, nontransformed human mammary epithelial cells, which have a much greater sensitivity to genistein, would be a better system for the study of these mechanisms.

美国《营养杂志》，1995年

金雀异黄素在肿瘤细胞中的生化指标评估

格雷格 彼得森

阿拉巴马大学生物化学系，伯明翰大学35294

虽然流行病学研究和癌症模型的数据表明，染料木黄酮在预防癌症中起着重要的作用，但染料木素作用的生化目标是未知的。染料木黄酮是蛋白酪氨酸激酶（PTK）活性的有效体外抑制剂，特别是表皮生长因子受体（EGF-R）的抑制剂，对丝氨酸/苏氨酸激酶几乎没有影响。这导致了染料木素可能通过抑制EGF-R PTK或其他关键PTK在体内的活性而发挥其抗癌作用的建议。随后对完整肿瘤细胞系的研究表明EGF-R和其他生长因子受体能够在染料木黄酮存在下传播有丝分裂信号。事实上，染料木素治疗后离散蛋白酪氨酸磷酸化的检测难度很大。已经从体外和细胞培养数据中提出了其他用于染料木黄酮作用的机制。染料木黄酮不仅在体外抑制纯化的拓扑异构酶II的活性，而且导致整个细胞中蛋白质相关单链断裂的积累。染料木黄酮还抑制可能导致组织损伤和DNA修饰的活性氧的产生。此外，染料木素作为弱雌激素，修饰细胞分化程序，抑制血管生成。调节细胞周期事件并可能引起细胞凋亡。然而，肿瘤细胞中以上几种机制对染料木素的生理学血清浓度敏感（<18.5Mumol / L，或<5微克/ mL）。初级，非转化的人类乳腺上皮细胞对染料木素具有更大的敏感性，将是研究这些机制的更好的系统。