EVALUATION OF THE BIOCHEMICAL TARGETS OF GENISTEIN IN TUMOR-CELLS
EVALUATION OF THE BIOCHEMICAL TARGETS OF GENISTEIN IN TUMOR-CELLS
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DOI：
10.1093/jn/125.suppl_3.784s
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发表时间：
1995-03-01
影响因子：
4.2
通讯作者：
PETERSON, G
中科院分区：
文献类型：
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作者：
PETERSON, G
尽管流行病学研究和癌症模型的数据表明染料木黄酮在癌症预防中起重要作用，但染料木黄酮作用的生化靶点尚不清楚。染料木黄酮是一种有效的体外蛋白酪氨酸激酶（PTK）活性抑制剂，尤其是表皮生长因子受体（EGF-R）的活性抑制剂，对丝氨酸/苏氨酸激酶几乎没有影响。这导致了染料木黄酮可能通过抑制EGF-R PTK或其他关键PTK在体内的活性来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素存在下传递促有丝分裂信号。事实上，很难检测到染料木素处理后离散蛋白质酪氨酸磷酸化的减少。从体外和细胞培养数据中已经提出了染料木黄酮作用的其他机制。Genistein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相关的单链断裂的积累。染料木黄酮还抑制可能导致组织损伤和DNA修饰的活性氧物质的产生。此外，染料木黄酮作为一种弱雌激素，改变细胞分化程序，抑制血管生成，调节细胞周期事件，并可能促进细胞凋亡。然而，肿瘤细胞中的上述机制很少对染料木素的生理血清浓度敏感（
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 (