Exploring MV14 as a nitric oxide-releasing strategy for bladder cancer: From synthesis to in vivo evaluation

Bladder cancer remains a significant clinical challenge due to high recurrence rates and limited therapeutic options. Herein, we report the synthesis and biological evaluation of MV14, a nitric oxide-releasing compound with promising antitumor activity against bladder cancer. MV14 reduced cell viability and inhibited proliferation in human bladder cancer cell lines, in a concentration- and cell line-dependent manner, showing a selectivity profile compared with non-malignant urothelial cells. Mechanistic studies revealed that its antiproliferative activity is associated with controlled nitric oxide (NO) release, likely leading to cell-cycle arrest and DNA damage. In addition, MV14 markedly inhibited NF-κB activation in a reporter cell system and reduced survivin levels in bladder cancer cells, suggesting interference with key survival-related pathways. Importantly, we provide the first in vivo evidence that a NO-releasing compound exhibits antitumor efficacy in an N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder cancer model, supporting its potential to modulate molecular mechanisms underlying tumorigenesis and disease progression. Together, these findings highlight MV14 as a promising candidate for the development of new intravesical therapeutic strategies against bladder cancer.