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

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.