Figure 8.

Schematic representation of the mechanisms underlying Etn-mediated metabolic stress in PCa cells. (A) The lipid bilayer of the cell membranes of cancer cells is more fluidic or less rigid. Glucose gets transported across the plasma membrane into the cytoplasm by GLUT1. Glucose metabolism through glycolysis (cytoplasm) and in mitochondria provides the energy required for cancer cells to meet their high energy and metabolic demands. (B) Etn treatment results in metabolic alterations in PCa cells. Etn lowers the glucose uptake into the cytosol by modulating GLUT1 trafficking, making PCa cells energy-deprived with increased metabolic stress. Etn increases the levels of PE in the membrane, making the membrane less fluidic (or more rigid). PE deacylation into GPE is enhanced, and PE/GPE ratio is decreased. The increased PE levels alter the mitochondrial structure and function and enhance lipolysis, leading to LD shrinkage and generation of fatty acids. The Etn-induced metabolic stress promotes autophagy, subsequently leading to apoptosis in PCa.