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Author Notes:

Correspondence to: Dr Xu Zhang, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TC M) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, P.R. China E‑ mail: zhangxutcm@yahoo.com

Jie Zhu and Meijuan Chen contributed equally to this work.


Research Funding:

This study was supported by the National Science and Technology Pillar Program in the 11th Five-year Plan of China 2006BAI11B08-01 (to H.F. and X.Z.), the U.S. National Institutes of Health grants P01 CA116676 (to H.F.), the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions (to X.Z.), China and Europe taking care of healthcare solutions, CHETCH Grant Agreement Number: PIRSES-GA-2013-612589 (to X.Z.) and the Natural Science Foundation of Jiangsu Province (BK20131415) (to M.C.).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • glycyrrhetinic acid
  • cell cycle arrest
  • ER stress
  • MICE

Glycyrrhetinic acid induces G1-phase cell cycle arrest in human non-small cell lung cancer cells through endoplasmic reticulum stress pathway

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Journal Title:

International Journal of Oncology


Volume 46, Number 3


, Pages 981-988

Type of Work:

Article | Final Publisher PDF


Glycyrrhetinic acid (GA) is a natural compound extracted from liquorice, which is often used in traditional Chinese medicine. The purpose of the present study was to investigate the antitumor effect of GA in human non-small cell lung cancer (NSCLC), and its underlying mechanisms in vitro. We have shown that GA suppressed the proliferation of A549 and NCI-H460 cells. Flow cytometric analysis showed that GA arrested cell cycle in G0/G1 phase without inducing apoptosis. Western blot analysis indicated that GA mediated G1-phase cell cycle arrest by upregulation of cyclin-dependent kinase inhibitors (CKIs) (p18, p16, p27 and p21) and inhibition of cyclins (cyclin-D1, -D3 and -E) and cyclin-dependent kinases (CDKs) (CDK4, 6 and 2). GA also maintained pRb phosphorylation status, and inhibited E2F transcription factor 1 (E2F-1) in both cell lines. GA upregulated the unfolded proteins, Bip, PERK and ERP72. Accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggered the unfolded protein response (UPR), which could be the mechanism by which GA inhibited cell proliferation in NSCLC cells. GA then coordinated the induction of ER chaperones, which decreased protein synthesis and induced cell cycle arrest in the G1 phase. This study provides experimental evidence to support the development of GA as a chemotherapeutic agent for NSCLC.

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© 2015, Spandidos Publications

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