尽管有各种治疗方法，但结直肠癌是全球死亡率最高的疾病之一。因此，开发新的、更有效的结直肠癌治疗方法至关重要。最近，反应性氧化物（ROS）/JNK信号通路被提议作为抗癌药物发现的潜在靶点。本研究调查了山竹中生物活性黄酮类甘草酮E（GAR E）的抗癌作用，并探讨其作用机制。HT-29和Caco-2癌细胞被用作体外模型研究GAR E的抗癌效应。研究结果表明，GAR E抑制了集落形成和创面愈合，同时触发了ROS的产生，导致线粒体功能障碍和凋亡，导致细胞周期在子G1阶段停滞。此外，GAR E处理提高了Bax/Bcl-2比值并激活了PARP、caspase 3和9和JNK1/2。这些GAR E诱导的细胞毒性活性和信号蛋白的表达可被抗氧化剂N-乙酰-L-半胱氨酸和JNK抑制剂SP600125逆转，表明ROS/JNK信号通路的参与。在HT-29异种移植裸鼠模型中的体内实验也证明了GAR E的抗肿瘤作用。总之，我们的发现表明GAR E可能在治疗结直肠癌方面具有潜在的有效性，并为黄酮作为新型化学治疗药物的发展提供了见解。版权所有©2023 Elsevier Masson SAS出版。

Despite various therapeutic approaches, colorectal cancer is among the most fatal diseases globally. Hence, developing novel and more effective methods for colorectal cancer treatment is essential. Recently, reactive oxygen species (ROS)/JNK signaling pathway has been proposed as the potential target for the anticancer drug discovery. The present study investigated the anticancer effects of the bioactive xanthone garcinone E (GAR E) in mangosteen and explored its underlying mechanism of action. HT-29 and Caco-2 cancer cells were used as in vitro models to study the anticancer effect of GAR E. The findings demonstrated that GAR E inhibited colony formation and wound healing, whereas triggered the production of ROS, which induced mitochondrial dysfunction and apoptosis, causing cell cycle arrest at the Sub G1 phase. Additionally, GAR E treatment elevated the ratio of Bax/Bcl-2 and activated PARP, caspases 3 and 9, and JNK1/2. These GAR E-induced cytotoxic activities and expression of signaling proteins were reversed by the antioxidant N-acetyl-L-cysteine and JNK inhibitor SP600125, indicating the involvement of ROS/JNK signaling pathways. In vivo experiments using an HT-29 xenograft nude mouse model also demonstrated the antitumor effect of GAR E. In conclusion, our findings showed that GAR E might be potentially effective in treating colorectal cancer and provided insights into the development of xanthones as novel chemotherapeutic agents.Copyright © 2023. Published by Elsevier Masson SAS.