Abstract
Aurora kinases, frequently detected to be over-expressing in human tumors, regulate many essential events during mitosis progression and have been regarded as potentially important targets for cancer therapy. S39 is a novel potent inhibitor of Aurora B kinase with the IC50 90.07 nM in the biochemical assay in an ATP competitive manner. S39 treatment on human tumor cells can inhibit the phosphorylation of Histone H3 (Ser10), a direct downstream substrate of Aurora B kinase, indicating S39 inhibits endogenous Aurora B kinase activity in cell-based level. Furthermore, S39 treatment blocks cell proliferation, inhibits colony formation and induces apoptosis in a wide range of human tumor cell lines. These results indicate that S39 is a potential lead compound to be an Aurora B inhibitor.
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This work was supported by The National 973 Program, 863 High Technology Program and the National Natural Science Foundation of China.
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10529_2013_1164_MOESM1_ESM.tif
Supplementary material 1 IC50 values of S39 on Aurora A and Aurora B kinase activity. Aurora A and Aurora B kinase were purchased from Invitrogen. Z’-LYTE™ Kinase Assay (Invitrogen) was performed to test the activity of Aurora A and Aurora B kinase with 25 nM kinase, 50 mM HEPES (pH 7.5), 1 mM EGTA, 10 mM MgCl2, ATP K m, 0.01 % Brij35, and 2 μM peptide as substrate for 1 h at 23 °C. For the IC50 test, 11 doses (100–0.1 μM) of the compound S39 were added to determine IC50. The readouts were analyzed using the Perkin–Elmer EnVision Workstation version 1.12. IC50 values were calculated using GraphPad Prism 5. S39 inhibits Aurora B kinase activity with the IC50 2.492 μM and inhibits Aurora A kinase activity with IC50 2.411 μM
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Li, J., Lang, Q., Zhang, H. et al. S39, a novel Aurora B kinase inhibitor, shows potent antineoplastic activity in human Hela cervical cancer cell line. Biotechnol Lett 35, 853–860 (2013). https://doi.org/10.1007/s10529-013-1164-z
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DOI: https://doi.org/10.1007/s10529-013-1164-z