Violacein as a multitarget agent in bladder cancer cells.

Violacein is a bacterial purple pigment with several biological activities, including anticancer. We previously showed its antiproliferative effect in cervical and bladder cancer cells. Here, we report quantitative differential proteomics in T24 bladder cancer cells, complemented with qRT-PCR of selected genes. Violacein treatment induced overproduction of proteins associated with tumor microenvironment remodeling, cell adhesion, immune response, apoptosis, autophagy, and cell cycle arrest. ICAM-1 emerged as a potential key driver, showing 24-fold gene overexpression and 6-fold protein overproduction, suggesting a protective role of violacein in enhancing immune cell infiltration into tumors. Violacein also reduced Annexin levels, which may limit their tumor-promoting and metastatic functions. Additionally, we identified proteins associated with better prognosis in cancer patients. Together, these findings highlight ICAM-1 as a central mediator of violacein's anticancer effects, and suggest that violacein is a multitarget agent that may modulate tumor microenvironment remodeling, tumor suppression, and immune responses. SIGNIFICANCE: Quantitative differential proteomics and qPCR analyses demonstrate that the bacterial pigment violacein functions as a multitarget agent capable of modulating multiple cancer-related pathways in the T24 bladder cancer cell line. Among these, violacein exerts tumor-suppressive effects by altering the tumor microenvironment and regulating immune-response pathways in bladder cancer cells, potentially contributing to improved patient prognosis.