Compound K [C-K; 20-O-(beta-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.
[1]Jilin Univ, Hosp 4, Gen Hosp First Automot Works, Dept Resp Med, Changchun 130011, Jilin, Peoples R China.
[2]Second Mil Med Univ, Changhai Hosp, Dept Resp & Crit Care Med, Shanghai 200433, Peoples R China.
[3]Jilin Univ, Hosp 1, Dept Gastroenterol, Changchun 130021, Jilin, Peoples R China.
(8.0+极速模式)