Induction of C/EBP homologous protein-mediated apoptosis and autophagy by licochalcone A in non-small cell lung cancer cells

  • Sci Rep. 2016 May 17;6:26241. doi: 10.1038/srep26241.
Zheng-Hai Tang  1 ,  Xin Chen  1 ,  Zhao-Yu Wang  1 ,  Ke Chai  1 ,  Ya-Fang Wang  1 ,  Xiao-Huang Xu  1 ,  Xiao-Wen Wang  2 ,  Jia-Hong Lu  1 ,  Yi-Tao Wang  1 ,  Xiu-Ping Chen  1 ,  Jin-Jian Lu  1
Affiliations
  • 1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
  • 2. Medical Center, Yuquan Hospital, Tsinghua University, Beijing, China.
PMID: 27184816 DOI: 10.1038/srep26241
Abstract

Licochalcone A (LCA), a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch, presents obvious anti-cancer effects. In this study, the anti-cancer effects and potential mechanisms of LCA in Non-Small Cell Lung Cancer (NSCLC) cells were studied. LCA decreased cell viability, increased Lactate Dehydrogenase release, and induced Apoptosis in a concentration-dependent manner in NSCLC cells while not in human embryonic lung fibroblast cells. The expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and formation of GFP-LC3 punta, two autophagic markers, were increased after treatment with LCA. LCA-induced LC3-II expression was increased when combined with chloroquine (CQ), while knock-down of Autophagy related protein (ATG) 7 or ATG5 reversed LCA-induced LC3-II expression and GFP-LC3 punta formation, suggesting that LCA induced Autophagy in NSCLC cells. Inhibition of Autophagy could not reverse the LCA-induced cell viability decrease and Apoptosis. In addition, LCA increased the expression of endoplasmic reticulum stress related proteins, such as binding immunoglobulin protein and C/EBP homologous protein (CHOP). Knock-down of CHOP reversed LCA-induced cell viability decrease, Apoptosis, and Autophagy. Taken together, LCA-induced autophagic effect is an accompanied phenomenon in NSCLC cells, and CHOP is critical for LCA-induced cell viability decrease, Apoptosis, and Autophagy.

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