Although numerous studies support a dose-effect relationship between
Endocrine disruptors (EDs) and the progression and
malignancy of
tumors, the impact of a chronic exposure to non-lethal concentrations of EDs in
cancer remains unknown. More specifically, a number of studies have reported the impact of
Aldrin on a variety of
cancer types, including
prostate cancer. In previous studies, we demonstrated the induction of the malignant phenotype in DU145
prostate cancer (PCa) cells after a chronic exposure to
Aldrin (an ED).
Proteins are pivotal in the regulation and control of a variety of cellular processes. However, the mechanisms responsible for the impact of ED on PCa and the role of
proteins in this process are not yet well understood. Here, two complementary computational approaches have been employed to investigate the molecular processes underlying the acquisition of
malignancy in
prostate cancer. First, the metabolic reprogramming associated with the chronic exposure to
Aldrin in DU145 cells was studied by integrating transcriptomics and metabolomics via constraint-based metabolic modeling. Second, gene set enrichment analysis was applied to determine (i) altered regulatory pathways and (ii) the correlation between changes in the transcriptomic profile of
Aldrin-exposed cells and
tumor progression in various types of
cancer. Experimental validation confirmed predictions revealing a disruption in metabolic and regulatory pathways. This alteration results in the modification of
protein levels crucial in regulating triacylglyceride/
cholesterol, linked to the malignant phenotype observed in
Aldrin-exposed cells.