期刊
CANCER LETTERS
卷 274, 期 1, 页码 72-77出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.08.033
关键词
Indirubin; 5 '-nitro-indirubinoxime; Cell cycle; PLK1; Apoptosis
类别
资金
- Korea Research Foundation
- Korean Government
- MOEHRD, Basic Research Promotion Fund [KRF-2007-331-C00208]
- National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea [0720430]
- MRC
- MOST/KOSEF [R13-2005-013-01000-0]
our previous study demonstrated that the novel indirubin derivative, 5'-nitro-indirubinoxime (5'-NIO), effectively at-rested the tumor growth through the inhibition of cell proliferation and the induction of apoptosis. However, the precise molecular mechanisms underlying 5'-NIO-induced antitumor activity remain unclear. Here, we report that 5'-NIO inhibits the proliferation of human KB oral carcinoma cells via the cell cycle arrest in G2/M phase. 5'-NIO reduced the activity of Cdc2/cyclin B complex through the inhibition of the PLK1 expression. Partially, 5'-NIO also arrested cell cycle in G1/S phase via the reduction of CDK4 and cyclin D1/D3 levels by p16 and induction of the level of p21(waf1). Using flow cytometry analysis, we showed that 5'-NIO-induced cell cycle arrest is followed by apoptosis. We determined further that 5'-NIO-induced apoptosis is accomplished by the mitochondira-dependent activation of the caspase cascade. Overall, these observations suggest the potential value of 5'-NIO as a candidate for a therapeutic modality for the treatment of oral cancer. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
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