A Multi-Level Systems Biology Analysis of Aldrin's Metabolic Effects on Prostate Cancer Cells

Area of Science:

• Environmental Toxicology
• Cancer Biology
• Computational Biology

Background:

• Endocrine disruptors (EDs) are linked to tumor progression, but chronic low-dose effects remain unclear.
• Aldrin, an ED, has been shown to impact various cancers, including prostate cancer (PCa).
• Previous work demonstrated Aldrin induces a malignant phenotype in DU145 PCa cells.

Purpose of the Study:

• To investigate the molecular mechanisms of ED-induced PCa malignancy.
• To understand the role of protein alterations in ED-mediated cancer progression.
• To explore metabolic and regulatory pathway changes in Aldrin-exposed PCa cells.

Main Methods:

• Integrated transcriptomics and metabolomics using constraint-based metabolic modeling.
• Gene set enrichment analysis to identify altered pathways and transcriptomic correlations.
• Experimental validation of computational predictions.

Main Results:

• Chronic Aldrin exposure caused significant metabolic reprogramming in DU145 PCa cells.
• Identified disruptions in key metabolic and regulatory pathways.
• Observed alterations in protein levels involved in triacylglyceride/cholesterol regulation, linked to malignancy.

Conclusions:

• Aldrin exposure disrupts cellular metabolism and regulatory pathways in prostate cancer.
• Altered protein levels, particularly in lipid metabolism, contribute to the malignant phenotype.
• These findings elucidate molecular pathways affected by chronic ED exposure in cancer.