title: The dietary flavonoid luteolin inhibits Aurora B kinase activity and blocks proliferation of cancer cells.
abstract: 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 (IC(50)=0.357 μM) and bind to Aurora B with a high affinity (K(D)=5.85 μM) 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.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Lang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.forename: Haoxing
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhishun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Wan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000494:pharmacology*; D064107:Aurora Kinase B; D064127:Aurora Kinases; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D056945:Hep G2 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D047311:Luteolin / Q000494:pharmacology*; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011874:Radiometry; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012694:Serine; D020349:Surface Plasmon Resonance; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006657:Histones; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D012694:Serine; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D047311:Luteolin