A new molecular mechanism underlying the EGCG-mediated autophagic modulation of AFP in HepG2 cells

Epigallocatechingallate (EGCG) is a major bioactive component of green tea and is associated with health benefits against multiple diseases including cancer. As an indicator of hepatocellular carcinoma (HCC), high levels of α-fetal protein (AFP) are related to malignant differentiation and poor prognosis of cancer cells. In this study, EGCG can effectively reduce AFP secretion and simultaneously induce AFP aggregation in human HCC HepG₂ cells. EGCG-stimulated autophagy induces the degradation of AFP aggregates in HepG₂ cells. Furthermore, we thoroughly studied the underlying molecular mechanisms behind EGCG-stimulated autophagy by using large-scale all-atom molecular dynamics simulations, which revealed a novel molecular mechanism. EGCG directly interacts with LC3-I protein, readily exposing the pivotal Gly-120 site of the latter to other important binding partners such as 1,2-distearoyl-sn-glycero-3-phosphoethanolamine and promoting the synthesis of LC3-II, a characteristic autophagosomal marker. Our results suggest that EGCG is critical in regulating AFP secretion and in modulating autophagic activities of HepG₂ cells, providing a molecular basis for potentially preventing and treating HCC.