Synergistic Solutions: Exploring Clotrimazole’s Potential in Prostate and Bladder Cancer Cell Lines

Abstract

Clotrimazole (CLZ), traditionally an antifungal agent, unveils promising avenues in cancer therapy, particularly in addressing bladder and prostate cancers. In vitro assessments underscore its remarkable efficacy as a standalone treatment, significantly diminishing cancer cell viability. Mechanistically, CLZ operates through multifaceted pathways, including the inhibition of Ca2+-dependent K+ channels, suppression of glycolysis-related enzymes, and modulation of the ERK-p65 signaling cascade, thus underscoring its potential as a versatile therapeutic agent. Our investigation sheds light on intriguing observations regarding the resilience of UM-UC-5 bladder cancer cells against high doses of paclitaxel (PTX), potentially attributed to heightened levels of the apoptosis-regulating protein Mcl-1. However, synergistic studies demonstrate that the combination of Doxorubicin (DOXO) and CLZ emerges as particularly potent, especially in prostate cancer contexts. This effectiveness could be associated with the inhibition of drug efflux mediated by multidrug resistance-associated protein 1 (MRP1), underscoring the importance of exploring combination therapies in cancer treatment paradigms. In essence, our findings shed light on the anticancer potential of CLZ, emphasizing the significance of tailored approaches considering specific cancer types and molecular pathways in drug repurposing endeavors. While further validation and clinical exploration are warranted, the insights gleaned from this study offer promising prospects for enhancing cancer therapy efficacy.