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, led to G1 phase arrest and apoptosis in A549 and H1975 cells. Subsequently, C-K promoted autophagy as confirmed by enhanced rate of positive acridine orange staining cells, increased LC3II and Beclin-1 levels, while decreased p62 level in A549 and H1975 cells. Moreover, 3-Methyladenine (3-MA, an inhibitor of autophagy) effectively suppressed proliferation inhibition and apoptosis induced by C-K. Finally, C-K treatment promoted the activation of AMPK/mTOR and JNK signaling pathways. Treatment with compound C (AMPK inhibitor) or SP600125 (JNK inhibitor) significantly restrained C-K-induced proliferation inhibition, apoptosis and autophagy 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.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author