Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Advanced Drug Preparation Technologies (Zhengzhou University), Ministry of Education of China, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Advanced Drug Preparation Technologies (Zhengzhou University), Ministry of Education of China, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
Bioorg Chem. 2019 Jun;87:688-698. doi: 10.1016/j.bioorg.2019.03.072. Epub 2019 Apr 4.
Sanggenon O (SO) is a Diels-Alder type adduct extracted fromMorus alba, which has been used for its anti-inflammatory action in the Oriental medicine. However, whether it has regulatory effect on human cancer cell proliferation and what the underlying mechanism remains unknown. Here, we found that SO could significantly inhibit the growth and proliferation of A549 cells and induce its pro-apoptotic action through a caspase-dependent pathway. It could also impair the mitochondria which can be reflected by mitochondrial membrane permeabilization. Besides, SQSTM1 up-regulation and autophagic flux measurement demonstrated that exposure to SO led to autophagosome accumulation, which plays a protective role in SO-treated cells. In addition, knocking down of LC3B increased SO triggered apoptotic cell rates. These results indicated that SO has great potential as a promising candidate combined with autophagy inhibitor for the treatment of NSCLC. In conclusion, our results identified a novel mechanism by which SO exerts potent anticancer activity.
桑根酮 O（SO）是从桑白皮中提取的一种 Diels-Alder 型加合物，在东方医学中已被用于抗炎作用。然而，它是否对人类癌细胞的增殖有调节作用，其潜在的机制尚不清楚。在这里，我们发现 SO 可以显著抑制 A549 细胞的生长和增殖，并通过半胱天冬酶依赖性途径诱导其促凋亡作用。它还可以损害线粒体，这可以通过线粒体膜通透性来反映。此外，SQSTM1 的上调和自噬流测量表明，暴露于 SO 会导致自噬体的积累，这在 SO 处理的细胞中起到保护作用。此外，敲低 LC3B 会增加 SO 引发的凋亡细胞比例。这些结果表明，SO 作为一种有前途的候选药物，与自噬抑制剂联合使用，可能对非小细胞肺癌的治疗具有巨大潜力。总之，我们的研究结果确定了 SO 发挥强大抗癌活性的一种新机制。
