The dietary flavonoid luteolin inhibits Aurora B kinase activity and blocks proliferation of cancer cells

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• 作者：Fang Xie^a ; Qingyu Lang^b ; Mei Zhou^a ; Haoxing Zhang^c ; Zhishun Zhang^a ; Yifeng Zhang^a ; Bo Wan^a ; Qiang Huang^a ; Long Yu^a ; ^{longyu@fudan.edu.cn}
• 关键词：HTS ; high-throughput screen ; FBS ; fetal bovine serum ; INCENP ; inner centromere protein ; MBP ; myelin basic protein ; IC50 ; the half of maximal inhibitory concentration ; SPR ; surface plasmon resonance ; PBS ; phosphate buffered saline ; TBS ; tris buffered salin
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2012
• 期刊代码：15_09280987
• 类别：pha
• 出版时间：15 August, 2012
• 卷：46
• 期：5
• 页码：388-396
• 文件大小：853 K

摘要

In human, Aurora B is a chromosomal passenger protein that induces phosphorylation of histone and involves in spindle checkpoint and cytokinesis. Aberrant expression of Aurora B has been shown to correlate with genetic instability and carcinogenesis. In the past, Aurora B has been validated as a drug target by several studies. Here we report that the dietary flavonoid luteolin could inhibit recombinant Aurora B in radiometric activity assay (IC₅₀ = 0.357 渭M) and bind to Aurora B with a high affinity (K_D = 5.85 渭M) measured by Biacore 3000. Dose-dependent down-regulation of phosphorylation on Ser10 of histone H3 was also observed in cancer cell lines after 24-h treatment, indicating that endogenous Aurora B activity was inhibited by luteolin. Furthermore, we evaluated the effects of luteolin on the survival of a panel of 23 cell lines, and found that luteolin blocked growth of HeLa cells and SW620 cells in an 8-day cell proliferation assay as well as in colony formation assay. Thus, we identified Aurora B as a novel direct target of luteolin, and our results demonstrated that targeting Aurora B by natural products may be a feasible strategy to develop low toxic anticancer agents.