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Article

Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling

  • Authors:
    • San-Yuan Chen
    • Chun-Hsiang Lin
    • Jiun-Tsai Lin
    • Yi-Fang Cheng
    • Han-Min Chen
    • Shao-Hsuan Kao
  • View Affiliations / Copyright

    Affiliations: Department of Traditional Chinese Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 600, Taiwan R.O.C., Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 402, Taiwan R.O.C., Institute of Applied Science and Engineering, Catholic Fu Jen University, New Taipei 242, Taiwan R.O.C., Energenesis Biomedical Co. Ltd., New Taipei 235, Taiwan R.O.C.
  • Pages: 5575-5580
    |
    Published online on: September 6, 2017
       https://doi.org/10.3892/ol.2017.6890
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Abstract

AMP-activated protein kinase (AMPK) is known as a pivotal regulator of cellular metabolism. Mounting evidences have demonstrated that AMPK activation exerts tumor suppressive activity on leukemia cells. The present study reported that adenine, an AMPK activator, triggers cell cycle arrest and autophagy of human chronic myelogenous leukemia K562 cells consequently suppressing cell viability. The present findings revealed that adenine treatment (4.0-8.0 mM) significantly inhibited the viability of K562 cells to 69.3±2.5% (24 h) and 53.4±2.1% (48 h) of the control. Flow cytometric analysis revealed that there was a significant accumulation in G2/M phase, but not sub-G1 phase K562 cells following exposure to adenine. Additional investigation demonstrated that adenine treatments significantly increased the number of acidic vesicular organelles and the level of autophagosomal microtubule associated protein 1 light chain 3 α (LC3) marker. By contrast, cleavage of caspase-9, caspase-3 and poly-ADP-ribose polymerase was insignificantly affected in K562 cells following adenine treatment. In K562 cells, adenine was able to markedly promote the phosphorylation of AMPKα and suppress the phosphorylation of mammalian target of rapamycin (mTOR), a downstream target of AMPK. In addition, inhibiting AMPK phosphorylation using dorsomorphin restored mTOR phosphorylation, inhibited the accumulation of LC3 and significantly recovered the suppressed cell viability in response to adenine. Taken together, the present results demonstrated that adenine induced G2/M phase arrest and autophagic cell death, consequently suppressing the viability of K562 cells, which may attribute to the AMPK activation triggered by adenine. These findings provide evidence that adenine may be beneficial to chronic myelogenous leukemia therapy by suppressing excessive cell proliferation.
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Copy and paste a formatted citation
Spandidos Publications style
Chen S, Lin C, Lin J, Cheng Y, Chen H and Kao S: Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling. Oncol Lett 14: 5575-5580, 2017.
APA
Chen, S., Lin, C., Lin, J., Cheng, Y., Chen, H., & Kao, S. (2017). Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling. Oncology Letters, 14, 5575-5580. https://doi.org/10.3892/ol.2017.6890
MLA
Chen, S., Lin, C., Lin, J., Cheng, Y., Chen, H., Kao, S."Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling". Oncology Letters 14.5 (2017): 5575-5580.
Chicago
Chen, S., Lin, C., Lin, J., Cheng, Y., Chen, H., Kao, S."Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling". Oncology Letters 14, no. 5 (2017): 5575-5580. https://doi.org/10.3892/ol.2017.6890
Copy and paste a formatted citation
x
Spandidos Publications style
Chen S, Lin C, Lin J, Cheng Y, Chen H and Kao S: Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling. Oncol Lett 14: 5575-5580, 2017.
APA
Chen, S., Lin, C., Lin, J., Cheng, Y., Chen, H., & Kao, S. (2017). Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling. Oncology Letters, 14, 5575-5580. https://doi.org/10.3892/ol.2017.6890
MLA
Chen, S., Lin, C., Lin, J., Cheng, Y., Chen, H., Kao, S."Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling". Oncology Letters 14.5 (2017): 5575-5580.
Chicago
Chen, S., Lin, C., Lin, J., Cheng, Y., Chen, H., Kao, S."Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling". Oncology Letters 14, no. 5 (2017): 5575-5580. https://doi.org/10.3892/ol.2017.6890
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