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NCPMF-60 induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells.
MedLine Citation:
PMID:  20948430     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
We recently established that NCPMF-60, a newly synthesized flavonoid, is an active cytotoxic component. The molecular mechanisms by which NCPMF-60 exerts its cytotoxic activity are currently unknown. In this study, we show that NCPMF-60 induces G2/M phase arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. After treatment of HepG2 cells with NCPMF-60, cell cycle-related proteins, such as cyclin B1, cyclin H, CDK7, and p-CDK1 (Thr161), were downregulated, whereas p21 and p-CDK1 (Thr14/Tyr15) were upregulated. The activity of CDK1/cyclinB complex was also inhibited by NCPMF-60. In addition, we observed poly(ADP-ribose) polymerase cleavage and activation of caspase 3 and caspase 9. The expression ratio of Bax/Bcl-2 was increased in the treated cells, in which Bax was also upregulated. We also found that the expression of p53 and its phosphorylation at Ser15 accumulated after the treatment of NCPMF-60. Moreover, upregulation of p21, p53-upregulated modifier of apoptosis, and Bax, three p53-target gene products, and the downregulation of Bcl-2 and MDM2, were observed in NCPMF-60-treated cells. However, p53 is not the only regulator in the stimulation of NCPMF-60 on p21 transcriptional level and posttranscriptional level. These results suggested that NCPMF-60 indeed activated the p53 pathway, which may contribute to its induction of cell cycle arrest and apoptosis in HepG2 cells. Collectively, our findings show that cell cycle arrest and apoptosis induced by NCPMF-60 was associated with the activation of p53 pathway and the inhibition of CDK-activating kinase activity in HepG2 cells.
Authors:
Qin-Sheng Dai; Wei Liu; Xiao-Bing Wang; Na Lu; Dan-Dan Gong; Ling-Yi Kong; Qing-Long Guo
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  22     ISSN:  1473-5741     ISO Abbreviation:  Anticancer Drugs     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-11-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  46-57     Citation Subset:  IM    
Affiliation:
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 2, People's Republic of China.
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