Aurora kinase A plays an essential role in mitosis including chromosome separation and cytokinesis. Aberrant expression and activity of Aurora kinase A is associated with numerous malignancies including colorectal cancer followed by poor prognosis. The aim of this study is to determine the inhibitory effects of LDD970, an indirubin derivative, on Aurora kinase A in HT29 colorectal cancer cells. In vitro kinase assay revealed that, LDD970 inhibited levels of activated Aurora kinase A (IC50=0.37 mM). The inhibitory effects of LDD970 on Aurora kinase A, autophosphorylation and phosphorylation of histone H3 (Ser10), were confirmed by immunoblot analysis. Moreover, LDD970 inhibited migration of HT29 cells and upregulated apoptosis-related protein cleaved PARP. In cell viability assay, LDD970 was observed to suppress HT29 cell growth (GI50=4.22 µM). Although further studies are required, results of the present study suggest that LDD970 provide a valuable insight into small molecule indirubin derivative for therapeutic potential in human colorectal cancer.

中文翻译：

---

靛玉红衍生物 LDD970 作为小分子极光激酶 A 抑制剂在人结肠直肠癌细胞中的表征

极光激酶 A 在包括染色体分离和胞质分裂在内的有丝分裂中起重要作用。Aurora 激酶 A 的异常表达和活性与包括结直肠癌在内的多种恶性肿瘤相关，预后不良。本研究的目的是确定 LDD970（一种靛玉红衍生物）对 HT29 结肠直肠癌细胞中的极光激酶 A 的抑制作用。体外激酶测定显示，LDD970 抑制活化的极光激酶 A 的水平（IC50=0.37 mM）。LDD970 对 Aurora 激酶 A、自磷酸化和组蛋白 H3 (Ser10) 磷酸化的抑制作用通过免疫印迹分析得到证实。此外，LDD970 抑制 HT29 细胞的迁移并上调凋亡相关蛋白裂解的 PARP。在细胞活力测定中，观察到 LDD970 抑制 HT29 细胞生长 (GI50=4.22 µM)。