Lung Chan1, Yao-Cheng Wu1, Chia-Ying Yu1, Ya-Chuan Chang1, Tzuo-Yi Hsieh1,2, Sung-Lang Chen1,2, Wen-Wei Sung1,2,*
1School of Medicine, Chung Shan Medical University, Taichung, Taiwan, 40201; 2Department of Urology, Chung Shan Medical University Hospital, Taichung, Taiwan, 40201; *Corresponding author
Purpose: Urothelial carcinoma (UC) encompasses about 90% of all bladder cancers. The main treatment is transurethral resection of the bladder tumor, followed by intravesical drug instillation. High rates of bladder cancer mortality, recurrence, and progression have intensified the search for alternative adjuvant therapies. Our aim in this study was to investigate the potential of melatonin as an adjuvant therapy in bladder cancer.
Materials and Methods: The UC cell lines T24 and UMUC3 were used for cell assays and cell cycle analysis via flow cytometry to analyze the effects of melatonin. Potential signaling pathways were investigated by protein arrays and confirmed by western blotting. The statistical significance of differences was set at p < 0.05.
Results: Melatonin treatment of T24 and UMUC3 bladder cancer cells significantly reduced cell proliferation and clonogenic ability, as determined by MTT assays and colony formation. Flow cytometry after a 24 or 48 h melatonin (2 mM) treatment revealed a significant accumulation of UMUC3 cells in the sub-G1 cell cycle stage and G1 arrest induction in T24 cells compared to the control group. Cell model experiments showed that melatonin suppresses the NF-κB/p65/HIF-1a pathway to regulate downstream proteins related to cell cycle regulation, induction of apoptosis, and inhibition of the epithelial–mesenchymal transition.
Conclusion: These findings provide evidence that melatonin could suppress tumor malignancy through the NF-κB/p65/HIF-1a pathway, thereby supporting a potential therapeutic role for melatonin in UC.