Chaetominine induces cell cycle arrest in human leukemia K562 and colon cancer SW1116 cells

  • Authors:
    • Jingyun Yao
    • Jianbo Xiao
    • Xing Wei
    • Yanhua Lu
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  • Published online on: July 17, 2018     https://doi.org/10.3892/ol.2018.9161
  • Pages: 4671-4678
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Abstract

Chaetominine 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 G1‑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 G1‑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.
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October-2018
Volume 16 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Yao J, Xiao J, Wei X and Lu Y: Chaetominine induces cell cycle arrest in human leukemia K562 and colon cancer SW1116 cells. Oncol Lett 16: 4671-4678, 2018
APA
Yao, J., Xiao, J., Wei, X., & Lu, Y. (2018). Chaetominine induces cell cycle arrest in human leukemia K562 and colon cancer SW1116 cells. Oncology Letters, 16, 4671-4678. https://doi.org/10.3892/ol.2018.9161
MLA
Yao, J., Xiao, J., Wei, X., Lu, Y."Chaetominine induces cell cycle arrest in human leukemia K562 and colon cancer SW1116 cells". Oncology Letters 16.4 (2018): 4671-4678.
Chicago
Yao, J., Xiao, J., Wei, X., Lu, Y."Chaetominine induces cell cycle arrest in human leukemia K562 and colon cancer SW1116 cells". Oncology Letters 16, no. 4 (2018): 4671-4678. https://doi.org/10.3892/ol.2018.9161