The combination between two well-studied bioactive compounds melatonin and salicylic acid with proper modifications unexpectedly creates a sharp pair of “scissors” cutting off the vicious connection between inflammation and cancer by targeting a key contributor Signal Transducers and Activators of Transcription 3 (STAT3) in the two pathological processes. A representative compound P-3 with IC₅₀ values on each tested cell line ranging from 7.37 to 18.62 μM among the designed melatonin derivatives is equipped with the ability of curbing inflammation-promoting cancer by down-regulating the expression, activation and nuclear translocation of STAT3, breaking the feedforward loop of STAT3 activation by decreasing the expression of pro-tumorigenic cytokines, and inducing cell apoptosis through ROS triggered Cyto-c/Caspase-3 pathway. This study suggests that the melatonin derivative P-3 is likely to become a promising chemical structure for developing the novel anti-cancer agents taking effect through hindering the mutual-promoting processes between inflammation and cancer.

两种经过充分研究的生物活性化合物褪黑激素和水杨酸经过适当修饰的组合意外地产生了一对锋利的“剪刀”，从而通过靶向关键的信号转导子和转录激活因子3（STAT3）切断了炎症和癌症之间的恶性联系。这两个病理过程。具有IC _50的代表性化合物P-3在设计的褪黑激素衍生物中，每个测试细胞系中的值介于7.37至18.62μM之间，具有通过下调STAT3的表达，激活和核易位，打破STAT3激活的前馈环来抑制促炎性癌症的能力。降低促肿瘤细胞因子的表达，并通过ROS诱导Cyto-c / Caspase-3途径诱导细胞凋亡。这项研究表明，褪黑激素衍生物P-3可能会成为一种有前景的化学结构，用于开发新型的抗癌药，通过阻止炎症和癌症之间的相互促进过程来发挥作用。