Effect of dexamethasone on biological properties and metabolic adaptations of normal prostate epithelial cells under mild serum conditions.

Limiting serum concentration in culture medium constitutes an environmental stress that disrupts cellular homeostasis and activates adaptive metabolism. This study aims to examine the impact of dexamethasone (DEX) on biological properties (e.g. viability, adhesion, migration) and glucose and lipid metabolism of prostate epithelial cells under stress conditions. The study used a non-tumorigenic human prostate cell line, PNT1A. In mild serum deprivation conditions, DEX, commonly used in the treatment of castration-resistant prostate cancer, also arrests normal prostate cells in the G0/G1 phase. Observed reduction in metabolic activity and limiting apoptosis of PNT1A cells as related to decreased expression of the NF-κB family and FOXO3 genes. Moreover, DEX modulated PNT1A migration by regulating cell plasticity thought capacity of adhesion to ECM proteins such as fibronectin and collagen I and IV. This was associated with changes in mRNA levels for the genes VIM, ZEB1 and ZEB2. Finally, it seems that dexamethasone helps PNT1A cells adapt to stress and enhance antioxidant defense, possibly by reprogramming lipid metabolism (e.g., LDLR, CPT1, MGLL), but not necessarily glucose metabolism.