Melatonin derivatives combat with inflammation-related cancer by targeting the Main Culprit STAT3.

ID: ALA4818998

Journal: Eur J Med Chem

Title: Melatonin derivatives combat with inflammation-related cancer by targeting the Main Culprit STAT3.

Authors: Ma S, Zhu L, Fan X, Luo T, Liu D, Liang Z, Hu X, Shi T, Tan W, Wang Z.

Abstract: 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.

CiteXplore: 33248852

DOI: 10.1016/j.ejmech.2020.113027

Patent ID: ┄