Induction of apoptosis and cell cycle arrest in glioma cells by GL331 (a topoisomerase II inhibitor).
BACKGROUND
GL331 is a topoisomerase II inhibitor and, in this study, the effects of GL331 upon rat C6 glioma cells were investigated.


METHODS
The glioma cells were treated with GL331, then a cytotoxicity assay was done to evaluate the cytotoxic effects of GL331 and flow-activated cell sorter analysis was performed to analyze the cellular apoptosis and cell cycle distribution of the glioma cells. The expressions of p53, p21 and 14-3-3sigma in glioma cells treated with GL331 were investigated by Western blot analysis.


RESULTS
GL331 was demonstrated to exert cytotoxic effects upon and induce apoptosis of the C6 glioma cells in a concentration- and time-dependent manner (p < 0.05). GL331 also caused the glioma cells to accumulate in the G2/M-phase of the cell cycle and increased the expressions of p53, p21 and 14-3-3sigma.


CONCLUSIONS
GL331 exerts cytotoxic effects and induces apoptosis in C6 glioma cells, accompanied by cell accumulation in the G2/M-phase and activation of p53, p21 and 14-3-3sigma.
Chen
Yun
Y
Department of Surgery, Far Eastern Memorial Hospital, 21, Sec. 2, Nan-Ya South Road, Pan-Chiao, Taipei 220, Taiwan.
Su
Yen-Hao
YH
Wang
Chih-Hsien
CH
Wu
Jiann-Ming
JM
Chen
Jin-Cherng
JC
Tseng
Sheng-Hong
SH
D048948:14-3-3 Proteins / Q000096:biosynthesis; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000031:analogs & derivatives* / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D059005:Topoisomerase II Inhibitors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D048948:14-3-3 Proteins; D000972:Antineoplastic Agents, Phytogenic; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D016159:Tumor Suppressor Protein p53; C121391:GL 331; D005047:Etoposide