1. Sanggenon O induced apoptosis of A549 cells is counterbalanced by protective autophagy.
- Author
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Li ZR, Ma T, Guo YJ, Hu B, Niu SH, Suo FZ, Du LN, You YH, Kang WT, Liu S, Mamun M, Song QM, Pang JR, Zheng YC, and Liu HM
- Subjects
- A549 Cells, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Proliferation drug effects, Cell Survival drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Flavonoids chemical synthesis, Flavonoids chemistry, Humans, Membrane Potential, Mitochondrial drug effects, Molecular Conformation, Molecular Docking Simulation, Protective Agents chemical synthesis, Protective Agents chemistry, Reactive Oxygen Species analysis, Reactive Oxygen Species metabolism, Structure-Activity Relationship, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Apoptosis drug effects, Autophagy drug effects, Flavonoids pharmacology, Protective Agents pharmacology
- Abstract
Sanggenon O (SO) is a Diels-Alder type adduct extracted fromMorus alba, which has been used for its anti-inflammatory action in the Oriental medicine. However, whether it has regulatory effect on human cancer cell proliferation and what the underlying mechanism remains unknown. Here, we found that SO could significantly inhibit the growth and proliferation of A549 cells and induce its pro-apoptotic action through a caspase-dependent pathway. It could also impair the mitochondria which can be reflected by mitochondrial membrane permeabilization. Besides, SQSTM1 up-regulation and autophagic flux measurement demonstrated that exposure to SO led to autophagosome accumulation, which plays a protective role in SO-treated cells. In addition, knocking down of LC3B increased SO triggered apoptotic cell rates. These results indicated that SO has great potential as a promising candidate combined with autophagy inhibitor for the treatment of NSCLC. In conclusion, our results identified a novel mechanism by which SO exerts potent anticancer activity., (Copyright © 2019. Published by Elsevier Inc.)
- Published
- 2019
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