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Ginsenoside metabolite compound K induces apoptosis and autophagy in non-small cell lung cancer cells via AMPK–mTOR and JNK pathways

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Compound K [C-K; 20-O-(β-d-glucopyranosyl)-20(S)-protopanaxadiol], as a metabolite of ginsenoside, has been verified to have antitumor effects in various cancers, including non-small cell lung cancer (NSCLC). However, the detailed mechanisms of C-K in NSCLC remain largely unknown. In this study, we aimed to evaluate the effect of C-K on apoptosis and autophagy in NSCLC cells as well as its related mechanisms. According to the results, C-K suppressed the proliferation, and led to G1 phase arrest and apoptosis in A549 and H1975 cells. Subsequently, C-K promoted autophagy, as confirmed by the enhanced rate of cells staining positive with acridine orange, increased levels of LC3II and Beclin-1, and with decreased levels of p62 in A549 and H1975 cells. Moreover, 3-methyladenine (3-MA; an inhibitor of autophagy) effectively suppressed the inhibition of proliferation and apoptosis that was induced with C-K. Finally, C-K treatment promoted the activation of the AMPK–mTOR and c-Jun N-terminal kinase (JNK) signaling pathways. Treatment with compound C (AMPK inhibitor) or SP600125 (JNK inhibitor) significantly restrained the inhibition of proliferation, apoptosis, and autophagy induced with C-K in A549 and H1975 cells. In conclusion, this study demonstrates that C-K promotes autophagy-mediated apoptosis in NSCLC via AMPK–mTOR and JNK signaling pathways.
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Keywords: AMPK–mTOR; apoptose; apoptosis; autophagie; autophagy; cancer pulmonaire non à petites cellules; composé K; compound K; non-small cell lung cancer

Document Type: Research Article

Affiliations: 1: Department of Respiratory and Critical Care Medicine, Changhai Hospital, The Second Military Medical University, Shanghai 200433, People’s Republic of China. 2: Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China. 3: Department of Respiratory Medicine, The General Hospital of First Automotive Works, The Fourth Hospital of Jilin University, Changchun 130011, People’s Republic of China.

Publication date: January 1, 2019

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