UM
Chaetominine induces cell cycle arrest in human leukemia K562 and colon cancer SW1116 cells
Yao, Jingyun; Xiao, Jianbo; Wei, Xing; Lu, Yanhua
2018-10
Source PublicationONCOLOGY LETTERS
ISSN1792-1074
Volume16Issue:4Pages:4671-4678
AbstractChaetominine is a cytotoxic alkaloid that has been demonstrated to promote apoptotic cell death in human leukemia K562 cells. In the present study, chaetominine inhibited K562 (IC50 34 nM) and SW1116 (IC50 46 nM) cell growth. However, it remains unclear whether the inhibition of cell growth is associated with the cell cycle. To assess this potential relationship, the effect of chaetominine on the cell cycle of K562 and SW1116 cells was examined. Chaetominine treatment caused cell apoptosis and G(1)-phase arrest in SW1116 cells. Conversely, K562 cells underwent S-phase arrest according to flow cytometric analysis. The present study also aimed to elucidate the molecular mechanisms underpinning cell cycle regulation following the incubation of the associated cells with chaetominine. Western blot and reverse transcription-quantitative polymerase chain reaction analyses suggested that chaetominine treatment facilitated the expression of p53, p21, checkpoint kinase 2 (Chk2) and phosphorylated ataxia telangiectasia mutated (p-ATM) and caused a reduction in the mRNA levels of cyclin E and cyclin-dependent kinases (CDKs) 2 and 4. These results suggest that chaetominine may be involved in the regulation of p53/p21 and ATM and Rad3-related (ATM)/Chk2 signaling in SW1116 cells. Previous studies have demonstrated that these signaling pathways are responsible for G(1)-phase arrest. Results of the present study demonstrated that the expression of p-ATR and Chk1 were increased in K562 cells. Additionally, cdc25A levels were decreased, while protein and gene expression levels of cyclin A and CDK2 were repressed. These results elucidated the role of chaetominine in in the regulation of ATR/cdc25A/Chk1 expression in K562 cells. These proteins are thus important determinants in the initiation of S-phase arrest. These data support the hypothesis that chaetominine is a potential anti-cancer therapeutic agent that targets the cell cycle.
Keywordcell cycle arrest cyclin cyclin-dependent kinase chaetominine K562 cells SW1116 cells
DOI10.3892/ol.2018.9161
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000444990700076
PublisherSPANDIDOS PUBL LTD
The Source to ArticleWOS
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Recommended Citation
GB/T 7714
Yao, Jingyun,Xiao, Jianbo,Wei, Xing,et al. Chaetominine induces cell cycle arrest in human leukemia K562 and colon cancer SW1116 cells[J]. ONCOLOGY LETTERS,2018,16(4):4671-4678.
APA Yao, Jingyun,Xiao, Jianbo,Wei, Xing,&Lu, Yanhua.(2018).Chaetominine induces cell cycle arrest in human leukemia K562 and colon cancer SW1116 cells.ONCOLOGY LETTERS,16(4),4671-4678.
MLA Yao, Jingyun,et al."Chaetominine induces cell cycle arrest in human leukemia K562 and colon cancer SW1116 cells".ONCOLOGY LETTERS 16.4(2018):4671-4678.
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