Prophylactic role of artemisinin in modulating FGFR3, HRAS, and TP53 to prevent early-stage urothelial carcinoma in BBN-induced mouse models

Abstract

Urinary bladder cancer remains a significant global health challenge, with effective early preventive strategies urgently needed to reduce incidence and progression. This study explores the prophylactic potential of artemisinin against N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced early-stage urothelial carcinoma in a mouse model. A multidisciplinary approach was used to evaluate artemisinin’s molecular and physiological effects. Techniques included protein–protein interaction (PPI) network analysis, molecular docking, gene expression profiling, histopathological evaluation, and systemic biomarker assessment. PPI analysis revealed FGFR3, HRAS, and TP53 as central oncogenic drivers. Molecular docking confirmed strong binding affinities of artemisinin to these targets. Prophylactic artemisinin administration significantly downregulated FGFR3 and HRAS while upregulating TP53, indicating early correction of carcinogenic signaling. These molecular changes were associated with preserved bladder and renal histoarchitecture, normalized kidney function markers, and restored hematological profiles, reflecting systemic protection against BBN-induced toxicity. Artemisinin effectively intercepts bladder carcinogenesis at multiple levels, modulating key genetic pathways and mitigating systemic damage. These findings provide compelling preclinical evidence supporting artemisinin as a promising prophylactic agent for bladder cancer prevention in high-risk populations.