Anesthetic pentobarbital inhibits proliferation and migration of malignant glioma cells.
Malignant gliomas are common and aggressive brain tumors in adults. The rapid proliferation and diffuse brain migration are main obstacles to successful treatment. Here we show that pentobarbital, a central depressant introduced clinically a century ago, is capable of suppressing proliferation and migration of C6 malignant glioma cells in a concentration-dependent manner. Pentobarbital also leads to a G1 phase cell cycle arrest accompanied by suppressed G1 cell cycle regulatory proteins Cyclin D1, Cyclin D3, CDK2 and phosphorylated Rb. In addition, noticeable morphological changes and interrupted alpha-tubulin microtubule assembly are induced by pentobarbital exposure. Intracellular signal pathways involved in the effect of pentobarbital is concerned with inactivation of ERK, c-Jun and Akt. Together, these findings suggest anti-proliferation and anti-migration effects of pentobarbital on malignant gliomas, most likely by arresting cell cycle and interfering microtubule. ERK, c-Jun MAPK and PI3K/Akt are possible signaling pathways involved.
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, Guangzhou, PR China.
Jun
J
Xie
Yan
Y
Li
Yijun
Y
Huang
Pengxin
P
Qiu
Minfeng
M
Shu
Wenbo
W
Zhu
Yanqiu
Y
Ou
Guangmei
G
Yan
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000503:physiopathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D018613:Microscopy, Confocal; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D014945:Wound Healing / Q000187:drug effects
D006993:Hypnotics and Sedatives; D010424:Pentobarbital