The effect of neonicotinoid insecticides and triazole fungicides on prostate cancer progression via CYP enzymes, miRNAs, and TF-mediated disruption of steroidogenesis: An integrated in silico approach.

Abstract

Neonicotinoid insecticides and triazole fungicides are widely used in agriculture, often in combination with other pesticides, leading to concerns about potential health effects. This study investigated the combined effect of these chemicals using the Comparative Toxicogenomics Database (CTD) to identify common target genes, followed by functional enrichment analysis and gene-gene and protein-protein interaction assessments. In this study, it was determined that pesticides may interfere with biological processes such as steroid hydroxylase activity, oxidoreductase activity, and steroid metabolism, and cause hormonal imbalances and endocrine system disorders. In addition, among the 10 genes identified, CYP3A5 and CYP3A7 gene expression differed significantly between prostate cancer and normal prostate tissues, and this was supported by UALCAN data. In addition, previous studies have confirmed that hsa-miR-27b, one of the prominent miRNAs in this study, and transcription factors (PROX1 and ESR2) are associated with prostate cancer. Similar to our study, previous studies have confirmed that triazole fungicides disrupt testosterone homeostasis and steroidogenesis, while neonicotinoids damage the prostate due to their effects on androgen receptors. These genes, miRNAs, and transcription factors appear to mediate the effects of these pesticides on cancer pathways and suggest a link to prostate cancer. In conclusion, this study demonstrated that concurrent exposure to neonicotinoid insecticides and triazole fungicides may damage the prostate and potentially contribute to the development of prostate neoplasia. These findings emphasise the importance of further in vitro and in vivo validation to establish a definitive causal relationship and provide insight into the toxicological effects of pesticide exposure on prostate health.