Colon cancer is one of the leading causes of cancer-related death in the world. The development of new drugs and therapeutic strategies for patients with colon cancer are urgently needed. Isodeoxyelephantopin (ESI), a sesquiterpene lactone isolated from the medicinal plant Elephantopus scaber L., has been reported to exert antitumor effects on several cancer cells. However, the molecular mechanisms underlying the action of ESI is still elusive. In the present study, we found that ESI potently suppressed cell proliferation in human colon cancer cells. Furthermore, our results showed that ESI treatment markedly increased cellular reactive oxygen species (ROS) levels by inhibiting thioredoxin reductase 1 (TrxR1) activity, which leads to activation of the JNK signaling pathway and eventually cell death in HCT116 and RKO cells. Importantly, we found that ESI markedly enhanced cisplatin-induced cytotoxicity in HCT116 and RKO cells. Combination of ESI and cisplatin significantly increased the production of ROS, resulting in activation of the JNK signaling pathway in HCT116 and RKO cells. In vivo, we found that ESI combined with cisplatin significantly suppressed tumor growth in HCT116 xenograft models. Together, our study provide a preclinical proof-of-concept for ESI as a potential strategy for colon cancer treatment.

结肠癌是世界上与癌症相关的死亡的主要原因之一。迫切需要为结肠癌患者开发新药和治疗策略。从药用植物中分离得到的倍半萜内酯-异去氧烯基肾上腺素（ESI）Elephantopus scaber据报道，L.L。对几种癌细胞具有抗肿瘤作用。然而，ESI作用的分子机制仍然难以捉摸。在本研究中，我们发现ESI可以有效抑制人结肠癌细胞中的细胞增殖。此外，我们的结果表明，ESI处理通过抑制硫氧还蛋白还原酶1（TrxR1）活性而显着增加了细胞活性氧（ROS）的水平，从而导致JNK信号通路的激活并最终导致HCT116和RKO细胞死亡。重要的是，我们发现ESI在HCT116和RKO细胞中显着增强了顺铂诱导的细胞毒性。ESI和顺铂的组合显着增加了ROS的产生，导致HCT116和RKO细胞中JNK信号通路的激活。体内，我们发现ESI与顺铂联合在HCT116异种移植模型中显着抑制了肿瘤的生长。总之，我们的研究为ESI提供了临床前的概念验证，可作为治疗结肠癌的潜在策略。