- Title
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Identifying tumor cell growth inhibitors by combinatorial chemistry and zebrafish assays
- Authors
- Xiang, J., Yang, H., Che, C., Zou, H., Yang, H., Wei, Y., Quan, J., Zhang, H., Yang, Z., and Lin, S.
- Source
- Full text @ PLoS One
Representative active compounds and resulted phenotypes. (A) Representative active compounds. Compounds 13-1-a, 13-1-e and 13-1-f are the most potent in zebrafish assay with the lowest effective concentration below 10 μM. (B) Embryonic phenotypes of compound treatment. a) control (10 hpf), b) control (24 hpf); c–e) show embryos treated with 20 μmol/L of 13-1-a (c), 13-1-e (d), and 13-1-f (e) and observed at 10 hpf (compounds were added at 5.5 hpf); f–h) show embryos at 24 hpf after the same treatment [13-1-a (f), 13-1-e (g), 13-1-f (h)]. Note smaller sizes compared control. (C) Compound 13-1-e has stronger effect on brain and eye development of zebrafish embryos. a) control (24 hpf), b) 13-1-e (20 μmol/L), c) 13-1-e (30 μmol/L), d) 13-1-e (40 μmol/L), 24 hpf; e) control (36 hpf), f) 13-1-e (20 μmol/L), g) 13-1-e (30 μmol/L), h) 13-1-e (40 μmol/L), 36 hpf. Compounds were added at 5.5 hpf. |
Kinase Assays. (A) The effects of compounds on purified recombinant CDK2/Cyclin E kinase activity to Histone H1; (B) The dose effect of 13-1-e on CDK2/Cycin E kinase activity; (C) The Dose effect of 13-1-a on CDK2/Cyc E kinase activity; (D) The Effect of 13-1-a and 13-1-e on the ERK2 kinase activity towards MBP. |
In vivo anti-tumor activity. (A) Compound 13-1-e inhibits proliferation of mouse colon tumor cell line CT26 in vitro. The number of cells treated with 0.3% DMSO serves as the control here. Red fluorescence represents the nuclei revealed by PI staining. (B) Average tumor size of CT26 cells injected in five mice followed by injections of ten doses of DMSO (50 μl) or 13-1-e (dissolved in 50 μl DMSO, 12.5 mg/kg for every two days) are 821 (±345) mm3 (DMSO) and 510 (±107) mm3 (13-1-e). P<0.05. |