Genistein is a specific inhibitor of protein tyrosine kinase (PTK) and is considered as a therapeutic candidate for various cancers. In this paper we investigate the effects of genistein on cell proliferation and differentiation in neuroblastoma (NB) cell lines and its possible mechanism of action. Genistein substantially inhibited the growth of five (N2A, JC, SKNSH, MSN and Lan5) of the six tumor cell lines examined in a dose-dependent manner with an IC50 value of approximately 5 microg/ml. The exception was GC cells. N2A cells were treated with genistein for 6 days and exhibited morphological features of differentiation, as evidenced by the development of dendritic extensions. Terminal deoxynucleotidyl transferase (TDT) histochemical staining showed a significant elevation in darkly stained nuclei in genistein-treated N2A cells compared with controls, indicating the occurrence of apoptosis. Fluorescent quantitation of DNA fragments confirmed apoptosis in genistein-treated N2A cells. To further elucidate the possible mechanisms by which genistein modulates NB cell growth and differentiation we investigated the effect of genistein on the activities of PTK and mitogen-activated protein (MAP) kinase and N-myc proto-oncogene expression in N2A cells. The results showed that genistein down-regulated intrinsic PTK activity by approximately 33% and inhibited insulin-like growth factor (IGF)-stimulated PTK activity by 75%. The effect of genistein on the intrinsic activity of MAP kinase was insignificant. In addition, genistein significantly reduced N-myc expression in a dose-dependent fashion. Our study suggests that genistein arrests cell growth and induces NB cell differentiation by mediating apoptosis and modulating PTK activity and N-myc proto-oncogene expression.

金雀异黄素是一个特定的蛋白酪氨酸激酶 （PTK）抑制剂，它被认为是治疗各种癌症的候选药物。 在本文中，我们调查金雀异黄素对神经母细胞瘤 (NB) 细胞系的抗增殖和诱导分化作用及其可能机制。 
金雀异黄素可大幅度的剂量依赖性地抑制试验中六分之五细胞系 (MSN，JC，SKNSH，N2A，和 Lan5）的生长 ，其IC50 值约为5微克/毫升，GC细胞系除外。N2A 细胞经金雀异黄素处理6 天后，显示形态学的分化特征，由发展的树突扩展可见一斑。 末端脱氧核糖核苷转移酶(TDT)组织化学染色表明，与控制组相比，金雀异黄素组在N2A 细胞染成黑的的细胞核中有显著的提高，这指示有细胞凋亡发生。DNA 片段的荧光定量检测证实金雀异黄素可诱导 N2A 细胞凋亡。 为了进一步解释金雀异黄素调节 NB 细胞生长和分化的可能的的机制，我们调查金雀异黄素对 PTK 和 (MAP) 丝裂素活化蛋白激酶活性及在 N2A 细胞中对 N-myc 原癌基因表达的影响。 结果显示金雀异黄素下调了内部 PTK 活性大约达 33%和抑制胰岛素样生长因子 (IGF)-受激的PTK 活性达75 %。 金雀异黄素对内部MAP 激酶活性的影响可忽略不计。 此外，金雀异黄素剂量依赖性地大大降低N-myc的表达。