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

• DOI: 10.1038/srep26241
• Publication Date: 2016-05-17T08:51:56Z
• Authors: Zheng-Hai Tang; Xin Chen; Zhao-Yu Wang; Ke Chai; Ya-Fang Wang; Xiao-Huang Xu; Xiao-Wen Wang; Jia-Hong Lu; Yi-Tao Wang; Xiu-Ping Chen; Jin-Jian Lu
• Keywords: 0303 health sciences; Lung Neoplasms; L-Lactate Dehydrogenase; Cell Survival; Apoptosis; Antineoplastic Agents, Phytogenic; Article; 3. Good health; 03 medical and health sciences; Chalcones; A549 Cells; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Gene Knockdown Techniques; Autophagy; Humans; Glycyrrhiza uralensis; Microtubule-Associated Proteins; Transcription Factor CHOP; Drugs, Chinese Herbal

AbstractLicochalcone 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.