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

doi:10.7150/ijms.42086

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24569

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24569

Title:	Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade
Authors:	Su, WW;Huang, JY;Chen, HM;Lin, JT;Kao, SH
Keywords:	apoptosis;hepatocellular cell;adenine;AMPK;p53;p21;Bax
Date:	2020
Issue Date:	2022-08-09T08:04:30Z (UTC)
Publisher:	IVYSPRING INT PUBL
ISSN:	1449-1907
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.
URI:	http://dx.doi.org/10.7150/ijms.42086 https://www.webofscience.com/wos/woscc/full-record/WOS:000519906700014 https://ir.csmu.edu.tw:8080/handle/310902500/24569
Relation:	INTERNATIONAL JOURNAL OF MEDICAL SCIENCES ,2020 ,v17 ,issue 5 ,p678-684
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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