AJMB  Vol.3 No.2 , April 2013
Effect of SP600125 on proliferation of embryonic stem cell
Abstract: SP600125 is an inhibitor of c-Jun NH2-terminal kinase (JNK), which plays a fundamental role in regulating animal development. Using SP600125 to deal with the mouse embryonic stem cells, it is revealed that the number of the ESC colonies decreased and the size became smaller. With treatment by SP600125, the proliferation of mouse ES cells is seriously inhibited for the cycle arrested in the G2/M phase, and the effect of SP600125 on the ES cells displays correlation of dose and time. The obtained results indicate that JNK may be an important regulator in the progression of cell cycle at the G2/M cell phase for the ES cells.
Cite this paper: Zhou, Y. , Jiang, M. , Wang, M. , Luo, C. , Wang, Z. , Wen, S. , Liu, W. and Xiao, Y. (2013) Effect of SP600125 on proliferation of embryonic stem cell. American Journal of Molecular Biology, 3, 67-71. doi: 10.4236/ajmb.2013.32009.

[1]   Hanks, S.K., Quinn, A.M. and Hunter, T. (1988) The protein kinase family: Conserved features and deduced phylogeny of the catalytic domains. Science, 241, 42-52. doi:10.1126/science.3291115

[2]   Gupta, S., Barrett, T.A., Whitmarsh, J., et al. (1996) Selective interaction of JNK protein kinase isoforms with transcription factors. The EMBO Journal, 15, 2760-2770.

[3]   Davis, R.J. (2000) Signal transduction by the JNK group of MAP kinases. Cell, 103, 239-252. doi:10.1016/S0092-8674(00)00116-1

[4]   Weston, C.R. and Davis, R.J. (2007) The JNK signal transduction pathway. Current Opinion in Cell Biology, 19, 142-149. doi:10.1016/

[5]   Bennett, B.L., Sasaki, D.T., Murray, B.W., et al. (2001) SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proceedings of the National Academy of Sciences of the USA, 24, 13681-13686. doi:10.1073/pnas.251194298

[6]   Han, Z.N., Boyle, D.L., Chang, L.F., et al. (2001) c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. Journal of Clinical Investigation, 1, 73-81.

[7]   Kuan, C.Y., Whitmarsh, A.J., Yang, D.D., et al. (2003) A critical role of neural-specific JNK3 for ischemic apoptosis. Proceedings of the National Academy Sciences of the USA, 25, 15184-15189. doi:10.1073/pnas.2336254100

[8]   Xie, Y., Puscheck, E.E. and Rappolee, D.A. (2006) Effects of SAPK/JNK inhibitors on preimplantation mouse embryo development are in fluenced greatly by the amount of stress induced by the media. Molecular Human Reproduction, 12, 217-224. doi:10.1093/molehr/gal021

[9]   Bernard, B., Heasley, L., et al. (2007) Concise review: Regulation of embryonic stem cell lineage commitment by mitogen-activated protein kinases. Stem Cells, 25, 1090-1095. doi:10.1634/stemcells.2006-0612

[10]   Abell, A.N., Granger, D.A. and Johnson, N.L. (2009) Trophoblast stem cell maintenance by fibroblast growth factor 4 requires MEKK4 activation of Jun N-terminal kinase. Molecular and Cellular Biology, 29, 2748-2761. doi:10.1128/MCB.01391-08

[11]   Kim, J.H., Lee, M.R., Kim, J.H., et al. (2008) IFATS collection: Selenium induces improvement of stem cell behaviors in human adipose-tissue stromal cells via SAPK/JNK and stemness acting signals. Stem Cells, 26, 2724-2734. doi:10.1634/stemcells.2008-0184

[12]   Tong, T., Fan, W., Zhao, H., et al. (2001) Involvement of the MAP kinase pathways in induction of GADD45 following UV radiation. Experimental Cell Research, 269, 64-72. doi:10.1006/excr.2001.5312

[13]   Tomioka, M., Nishimoto, M., Miyagi, S., et al. (2002) Identification of Sox-2 regulatory region which is under the control of Oct-3/4-Sox-2 complex. Nucleic Acids Research, 30, 3202-3213. doi:10.1093/nar/gkf435

[14]   Kiran, A., Rex, P., et al. (2006) The specific JNK inhibitor SP600125 targets tumour necrosis factor—A production and epithelial cell apoptosis in acute murine colitis. Immunology, 118, 112-121. doi:10.1111/j.1365-2567.2006.02349.x

[15]   Chen, F. (2012) JNK-induced apoptosis, compensatory growth, and cancer stem cells. Cancer Research, 2, 379-386. doi:10.1158/0008-5472.CAN-11-1982

[16]   Marie, A.B. and Bostjan, K. (2006) Uses for JNK: The many and varied substrates of the c-Jun N-terminal kinases. Molecular Cell, 70, 1061-1095.

[17]   Amy, M.M. and Marietta, P.M. (2004) Inhibition of JNK reduces G2/M transit independent of p53, leading to endoreduplication, decreased proliferation, and apoptosis in breast cancer cells. Oncogene, 23, 596-604. doi:10.1038/sj.onc.1207147

[18]   Brydon, L.B. and Dennis, T. (2001) SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. PNAS, 98, 13681-13686. doi:10.1073/pnas.251194298

[19]   Mohamed, J. and Ilio, V. (2012) Selective killing of p53-deficient cancer cells by SP600125. EMBO Molecular Medicine, 4, 1-15.

[20]   Moon, D.O., Kim, M.O., Choi Y.H., et al. (2008) Bcl-2 overexpression attenuates SP600125-induced apoptosis in human leukemia U937 cells. Cancer Letters, 264, 316-325. doi:10.1016/j.canlet.2008.02.011