Celastrol causes apoptosis and cell cycle arrest in rat glioma cells.
Glioma still remains a major health problem in the world. Celastrol has been proved to be an effective natural proteasome inhibitor and was used for treatment of autoimmune disease, chronic inflammation and neurodegenerative disease. However, its effect on glioma is unclear. In this study, we investigated the therapeutic effects of celastrol on C6 glioma cells. The results demonstrated that celastrol inhibited cell proliferation in a time- and dose-dependent manner, suppressed proteasome chymotrypsin-like activity and induced apoptosis and cell cycle arrest at G2/M phase in C6 cells. Proapoptosis proteins bax and caspase-3 were up-regulated, as well as cell cycle G2/M-related proteins cyclin B(1), p21 and p27. Conversely, anti-apoptosis proteins bcl-2 and XIAP and cell cycle regulator cyclin-dependent kinase 2 were down-regulated. Taken together, our data suggest that celastrol can suppress proteasome activity and induce apoptosis and cell cycle arrest in C6 glioma cells, which make it be a potential drug for glioma.
Ge
Pengfei
P
Department of Neurosurgery, First Hospital of Jilin University, Changchun, China.
Ji
Xunming
X
Ding
Yuchuan
Y
Wang
Xiaofei
X
Fu
Shuangliin
S
Meng
Fankai
F
Jin
Xin
X
Ling
Feng
F
Luo
Yinan
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001562:Benzimidazoles; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy* / Q000503:physiopathology / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D053978:Pentacyclic Triterpenes; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D051381:Rats; D013997:Time Factors; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D053978:Pentacyclic Triterpenes; D061988:Proteasome Inhibitors; D014315:Triterpenes; D046988:Proteasome Endopeptidase Complex; C050414:celastrol; C017807:bisbenzimide ethoxide trihydrochloride