A Surprising Repurposing of Central Nervous System Drugs against Squamous Cell Carcinoma of the Bladder, UM-UC-5

The potential benefits of drug repurposing have gained attention as an alternative to developing de novo drugs. The potential of using central nervous system (CNS) drugs as anticancer drugs has been explored in several types of human cancers, such as breast and colon cancer, among others. Here, we examine the effect of the CNS drugs sertraline, paroxetine, and chlorpromazine on human squamous carcinoma cells of the bladder (UM-UC-5). After exposing UM-UC-5 cells to increased concentrations of each drug for 48 h, we assessed their metabolic activity using an MTT assay. Based on those results, we calculated cell viability and the half-maximal inhibitory concentration (IC ) values. The results suggest that the CNS drugs were effective against UM-UC-5 in the order of potency of sertraline > chlorpromazine > paroxetine. Interestingly, sertraline was more potent than 5-fluorouracil (5-FU), a widely used anticancer drug. This study demonstrated, for the first time, the promising anticancer activity of CNS drugs on human bladder cancer cells in vitro and supports the repurposing of CNS drugs to improve cancer treatment. Nevertheless, further studies are necessary to understand their mechanism of action and in vivo activity.