Melatonin derivatives combat with inflammation-related cancer by targeting the Main Culprit STAT3
- Eur J Med Chem. 2021 Feb 5:211:113027. doi: 10.1016/j.ejmech.2020.113027.
- 1. School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
- 2. School of Pharmacy, Lanzhou University, Lanzhou, 730000, China. Electronic address: [email protected].
- 3. School of Pharmacy, Lanzhou University, Lanzhou, 730000, China. Electronic address: [email protected].
- 4. School of Pharmacy, Lanzhou University, Lanzhou, 730000, China; State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China. Electronic address: [email protected].
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.