a Department of Respiratory Medicine, The General Hospital of First Automotive Works, The Fourth Hospital of Jilin University, Changchun 130011, People's Republic of China.
b Department of Respiratory and Critical Care Medicine, Changhai Hospital, The Second Military Medical University, Shanghai 200433, People's Republic of China.
Biochem Cell Biol. 2019 Aug;97(4):406-414. doi: 10.1139/bcb-2018-0226. Epub 2018 Nov 26.
Compound K [C-K; 20--(β-d-glucopyranosyl)-20()-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.
化合物 K [C-K; 20--(β-d-吡喃葡萄糖基)-20()-原人参二醇]，作为一种人参皂苷的代谢产物，已被证实对多种癌症具有抗肿瘤作用，包括非小细胞肺癌（NSCLC）。然而，C-K 在 NSCLC 中的详细作用机制仍知之甚少。在这项研究中，我们旨在评估 C-K 对 NSCLC 细胞凋亡和自噬的影响及其相关机制。结果表明，C-K 抑制了 A549 和 H1975 细胞的增殖，并导致 G1 期阻滞和细胞凋亡。随后，C-K 促进了自噬，这一点通过吖啶橙染色阳性细胞的比率增加、LC3II 和 Beclin-1 水平升高以及 A549 和 H1975 细胞中 p62 水平降低得到证实。此外，3-甲基腺嘌呤（3-MA；自噬抑制剂）可有效抑制 C-K 诱导的增殖和凋亡抑制作用。最后，C-K 处理促进了 AMPK-mTOR 和 c-Jun N 端激酶（JNK）信号通路的激活。用化合物 C（AMPK 抑制剂）或 SP600125（JNK 抑制剂）处理可显著抑制 C-K 诱导的 A549 和 H1975 细胞增殖、凋亡和自噬的抑制作用。综上所述，本研究表明 C-K 通过 AMPK-mTOR 和 JNK 信号通路促进 NSCLC 中的自噬介导的细胞凋亡。
