Resveratrol Induces Autophagy and Apoptosis in Non-Small-Cell Lung Cancer Cells by Activating the NGFR-AMPK-mTOR Pathway

• Published in: Nutrients Vol. 14; no. 12; p. 2413
• Main Authors: Li, Jiaqiao, Fan, Yameng, Zhang, Yan, Liu, Yamei, Yu, Yan, Ma, Mao
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01-06-2022; MDPI
• Subjects: A549 cell line; Adenoviruses; Apoptosis; Autophagy; Autophagy (Cytology); Cancer; Cancer therapies; Care and treatment; Cell culture; Cell cycle; Cell growth; Cytokine receptors; Development and progression; Flow cytometry; Gene expression; Growth factors; Health aspects; Homeostasis; Kinases; Life span; Lung cancer; Lung cancer, Non-small cell; Metastasis; Nerve growth factor receptors; NGFR-AMPK-mTOR pathway; non-small-cell lung cancer; Oncology, Experimental; Penicillin; Protein kinases; Proteins; Resveratrol; Signal transduction; Survival; TOR protein; Tumors; China; Beijing China; United States > US
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu14122413

Resveratrol (RSV) has been reported to induce autophagy and apoptosis in non-small-cell lung cancer A549 cells, and the nerve growth factor receptor (NGFR) regulates autophagy and apoptosis in many other cells. However, the effect of NGFR on autophagy and apoptosis induced by RSV in A549 cells remains unclear. Here, we found that RSV reduced the cell survival rate in time- and concentration-dependent manners, activating autophagy and apoptosis. Lethal autophagy was triggered by RSV higher than 55 μM. The relationship between autophagy and apoptosis depended on the type of autophagy. Specifically, mutual promotion was observed between apoptosis and lethal autophagy. Conversely, cytoprotective autophagy facilitated apoptosis but was unaffected by apoptosis. RSV enhanced NGFR by increasing mRNA expression and prolonging the lifespan of NGFR mRNA and proteins. RSV antagonized the enhanced autophagy and apoptosis caused by NGFR knockdown. As the downstream pathway of NGFR, AMPK-mTOR played a positive role in RSV-induced autophagy and apoptosis. Overall, RSV-induced autophagy and apoptosis in A549 cells are regulated by the NGFR-AMPK-mTOR signaling pathway.