Int J Med Sci 2020; 17(5):678-684. doi:10.7150/ijms.42086 This issue Cite

Research Paper

Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade

Wei-Wen Su1, Jen-Yu Huang2, Han-Min Chen3, Jiun-Tsai Lin4, Shao-Hsuan Kao2,5,6✉

1. Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan.
2. Institute of Biochemistry, Microbiology, and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan.
3. Institute of Applied Science and Engineering, Catholic Fu Jen University, New Taipei 24205, Taiwan.
4. Energenesis Biomedical Co. Ltd., Taipei 11492, Taiwan.
5. Institute of Medicine, Chung Shan, Medical University, Taichung 40201, Taiwan.
6. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.

Citation:
Su WW, Huang JY, Chen HM, Lin JT, Kao SH. Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade. Int J Med Sci 2020; 17(5):678-684. doi:10.7150/ijms.42086. https://www.medsci.org/v17p0678.htm
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Abstract

Background: Adenine exhibits potential anticancer activity against several types of malignancies. However, whether adenine has anticancer effects on hepatocellular carcinoma (HCC) cells is incompletely explored.

Methods: Human HCC cell lines HepG2 and SK-Hep-1 (p53-wild type) and Hep3B (p53-deficient) were used as cell model. Cell growth and cell cycle distribution were determined using MTT assay and flow cytometric analysis, respectively. Protein expression and phosphorylation were assessed by Western blot. Involvement of AMP-activated protein kinase (AMPK) was evaluated using specific inhibitor and small inhibitory RNA (siRNA).

Results: Adenine treatments (0.5 - 2 mM) clearly decreased the cell growth of Hep G2 and SK-Hep-1 cells to 72.5 ± 3.4% and 71.3 ± 4.6% of control, respectively. In parallel, adenine also induced sub-G1 and S phase accumulation in both HCC cells. However, adenine did not affect the cell growth and cell cycle distribution of Hep3B cell. Western blot analysis showed that adenine reduced expression of cyclin A/D1 and cyclin-dependent kinase (CDK)2 and upregulated p53, p21, Bax, PUMA, and NOXA in HepG2 cell. Moreover, adenine induced AMPK activation that was involved in the p53-associated apoptotic cascade in HepG2 cells. Inhibition of AMPK activation or knockdown of AMPK restored the decreased cell growth of HepG2 and SK-Hep-1 cells in response to adenine.

Conclusions: These findings reveal that adenine reduces the cell growth of HepG2 and SK-Hep-1 but not Hep3B cells, attributing to the AMPK/p53-mediated S phase arrest and apoptosis. It suggests that adenine has anticancer potential against p53-wild type HCC cells and may be beneficial as an adjuvant for HCC treatment.

Keywords: apoptosis, hepatocellular cell, adenine, AMPK, p53, p21, Bax


Citation styles

APA
Su, W.W., Huang, J.Y., Chen, H.M., Lin, J.T., Kao, S.H. (2020). Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade. International Journal of Medical Sciences, 17(5), 678-684. https://doi.org/10.7150/ijms.42086.

ACS
Su, W.W.; Huang, J.Y.; Chen, H.M.; Lin, J.T.; Kao, S.H. Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade. Int. J. Med. Sci. 2020, 17 (5), 678-684. DOI: 10.7150/ijms.42086.

NLM
Su WW, Huang JY, Chen HM, Lin JT, Kao SH. Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade. Int J Med Sci 2020; 17(5):678-684. doi:10.7150/ijms.42086. https://www.medsci.org/v17p0678.htm

CSE
Su WW, Huang JY, Chen HM, Lin JT, Kao SH. 2020. Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade. Int J Med Sci. 17(5):678-684.

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