Total ginsenosides extract induce autophagic cell death in NSCLC cells through activation of endoplasmic reticulum stress

Ethnopharmacological relevance: Ginseng (Panax ginseng C. A. Mey) has been widely used in Asian countries for thousands of years. It has auxiliary anticancer efficacy and its derived preparations (e.g. Shenmai injection) are prescribed for cancer patients as Traditional Chinese Medicines clinically in China.

Aim of the study: The involved adjuvant anticancer mechanisms of ginseng are still unknown. The present study evaluated the anti-cancer effect of total ginsenosides extract (TGS) and determined the anticancer mechanisms of TGS-induced cell death in human non-small cell lung cancer (NSCLC) cells.

Materials and methods: The anti-cancer effect of TGS was evaluated in NSCLC by cell proliferation assay. The autophagy flux induction of TGS were tested and validated by Western blot, immunofluorescence and transmission electron microscope. The mechanisms of TGS in inducing autophagic cell death were validated by Western blot, gene knockdown and quantitative real time PCR assay.

Results: We found TGS could induce cell death in concentration and time dependent manners, and the cell morphology of NSCLC changed from cobblestone shape to elongated spindle shape after treated with TGS. In the study of cell autophagy, we confirm that TGS could upregulate autophagy flux and induce autophagic cell death through activation endoplasmic reticulum stress. Further investigations demonstrated this process was mediated by the ATF4-CHOP-AKT1-mTOR axis in NSCLC cells.

Conclusion: Our findings suggested that TGS could induce autophagic cell death in NSCLC cells through activation of endoplasmic reticulum stress, disclosing another characteristic of TGS-induced cell death and a novel mechanism of TGS and its derived preparations in clinical treatment of cancer patients.