Hangzhou Medical College, Hangzhou 310014, China.
Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou 310014, China.
Molecules. 2022 Jul 8;27(14):4398. doi: 10.3390/molecules27144398.
Eurycomanone (EN) is one of the representative quassinoid diterpenoids from roots of Jack, a natural medicine that is widely distributed in Southeast Asia. Previous studies showed that EN induces cancer cell apoptosis and exhibits anti-cancer activity, but the molecular mechanism of EN against cancer has still not been elucidated. In this study, we examined the regulatory effect of EN on autophagy to reveal the mechanism of EN-mediated colon cancer growth inhibition. First, we found that EN is able to inhibit colon cancer cell proliferation and colony formation. The angiogenesis level in cancer cells was inhibited as well. Next, the treatment of EN led to the suppression of autophagy, which was characterized by the downregulation of the LC3-II level and the formation of GFP-LC3 puncta under EN treatment in colon cancer. Moreover, we revealed that the mTOR signaling pathway was activated by EN in a time- and concentration-dependent manner. Finally, autophagy induction protected colon cancer cells from EN treatment, suggesting that autophagy improves cell survival. Taken together, our findings revealed the mechanism of EN against colon cancer through inhibiting autophagy and angiogenesis in colon cancer, supporting that the autophagy inhibitor EN could be developed to be a novel anti-cancer agent.
柚皮苷（EN）是从东南亚广泛分布的天然药物 Jack 的根中提取的代表性三萜类化合物之一。先前的研究表明，EN 诱导癌细胞凋亡并具有抗癌活性，但 EN 对抗癌症的分子机制仍未阐明。在这项研究中，我们研究了 EN 对自噬的调节作用，以揭示 EN 介导的结肠癌生长抑制的机制。首先，我们发现 EN 能够抑制结肠癌细胞的增殖和集落形成。癌细胞中的血管生成水平也受到抑制。接下来，EN 的处理导致自噬的抑制，其特征在于在 EN 处理下 LC3-II 水平的下调和 GFP-LC3 斑点的形成。此外，我们揭示了 EN 以时间和浓度依赖的方式激活 mTOR 信号通路。最后，自噬诱导可保护结肠癌细胞免受 EN 处理，表明自噬可提高细胞存活率。总之，我们的研究结果通过抑制结肠癌中的自噬和血管生成揭示了 EN 对抗结肠癌的机制，支持将自噬抑制剂 EN 开发为新型抗癌药物。
