Anesthetic pentobarbital inhibits proliferation and migration of malignant glioma cells.
作者： Jun Xie , Yan Li , Yijun Huang , Pengxin Qiu , Minfeng Shu
DOI: 10.1016/J.CANLET.2009.02.055
关键词:
摘要: Abstract Malignant gliomas are common and aggressive brain tumors in adults. The rapid proliferation diffuse migration main obstacles to successful treatment. Here we show that pentobarbital, a central depressant introduced clinically century ago, is capable of suppressing C6 malignant glioma cells concentration-dependent manner. Pentobarbital also leads G1 phase cell cycle arrest accompanied by suppressed regulatory proteins Cyclin D1, D3, CDK2 phosphorylated Rb. In addition, noticeable morphological changes interrupted α-tubulin microtubule assembly induced pentobarbital exposure. Intracellular signal pathways involved the effect concerned with inactivation ERK, c-Jun Akt. Together, these findings suggest anti-proliferation anti-migration effects on gliomas, most likely arresting interfering microtubule. MAPK PI3K/Akt possible signaling involved.
elsevier.com
sci-hub.se 参考文章(48)
Susan M Chang, Michael D Prados, WK Alfred Yung, Howard Fine, Larry Junck, Harry Greenberg, H Ian Robins, Minesh Mehta, Karen L Fink, Kurt A Jaeckle, John Kuhn, Kenneth Hess, Clifford Schold, None, Phase II study of neoadjuvant 1, 3-bis (2-chloroethyl)-1-nitrosourea and temozolomide for newly diagnosed anaplastic glioma: a North American Brain Tumor Consortium Trial. Cancer. ,vol. 100, pp. 1712- 1716 ,(2004) , 10.1002/CNCR.20157
TG Hales, RF Tyndale, Few cell lines with GABAA mRNAs have functional receptors The Journal of Neuroscience. ,vol. 14, pp. 5429- 5436 ,(1994) , 10.1523/JNEUROSCI.14-09-05429.1994
Cecilio Alamo, Francisco López-Muñoz, Ronaldo Ucha-Udabe, The history of barbiturates a century after their clinical introduction Neuropsychiatric Disease and Treatment. ,vol. 1, pp. 329- 343 ,(2005)
Alf Giese, Michael E. Berens, Melinda A. Loo, Monique D. Rief, Determinants of Human Astrocytoma Migration Cancer Research. ,vol. 54, pp. 3897- 3904 ,(1994)
Douglas A Lauffenburger, Alan F Horwitz, Cell Migration: A Physically Integrated Molecular Process Cell. ,vol. 84, pp. 359- 369 ,(1996) , 10.1016/S0092-8674(00)81280-5
Jeffrey J. Olson, Craig Shelley, Kathryn Orr, Thomas DeLaney, Edward H. Oldfield, The cerebral radioprotective effect of alternative barbiturates to pentobarbital. Neurosurgery. ,vol. 30, pp. 720- 723 ,(1992) , 10.1097/00006123-199205000-00012
Mary Ann Jordan, Leslie Wilson, Microtubules as a target for anticancer drugs. Nature Reviews Cancer. ,vol. 4, pp. 253- 265 ,(2004) , 10.1038/NRC1317
Bruce F. Kimler, Changnian Liu, Richard G. Evans, Robert A. Morantz, Effect of pentobarbital on normal brain protection and on the response of 9L rat brain tumor to radiation therapy. Journal of Neurosurgery. ,vol. 79, pp. 577- 583 ,(1993) , 10.3171/JNS.1993.79.4.0577
Ying Wen, Christina H. Eng, Jan Schmoranzer, Noemi Cabrera-Poch, Edward J. S. Morris, Michael Chen, Bradley J. Wallar, Arthur S. Alberts, Gregg G. Gundersen, EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nature Cell Biology. ,vol. 6, pp. 820- 830 ,(2004) , 10.1038/NCB1160
A. Jussofie, V. Reinhardt, R. Kalff, GABA binding sites: their density, their affinity to muscimol and their behaviour against neuroactive steroids in human gliomas of different degrees of malignancy. Journal of Neural Transmission. ,vol. 96, pp. 233- 241 ,(1994) , 10.1007/BF01294790