The self-assembled alpha-lactalbumin-oleic acid complex inhibits ATP supply from both glycolysis and the TCA cycle in HepG2 cells and HepG2-bearing nude mice

摘要

Energy metabolism has been a predominant target for anti-cancer drug development. The self-assembled anti-tumor alpha-lactalbumin-oleic acid complex (alpha-LA-OA) affects the energy metabolism of tumor cells, however, the role of targeting energy metabolism in its anti-tumor mechanism still needs to be clarified. alpha-LA assembled with OA to form a complex with an average diameter of 144.1 +/- 7.241 nm, which is 10-fold larger than alpha-LA alone. Furthermore, the self- assembled alpha-LA-OA inhibited the ATP supply from both glycolysis and oxidative phosphorylation in HepG2 cells and HepG2-bearing nude mice. The gene expression of enzymes involved in glycolysis (HK2, aldose, PKM2, LDHB) and oxidative phosphorylation (CS, ACO2, IDH2, SDHA) was inhibited. This inhibitory effect was also evident by increased phosphorylation of AMPK alpha. alpha-LA-OA also suppressed the expression of HIF-1 alpha and increased the expression of activated caspase-3. These findings demonstrate that the anti-tumor mechanism of alpha-LA-OA may be related to its inhibitory effect on the ATP supply, which then activates programmed cell death pathways. This study also indicated that alpha-LA-OA is a potent anti-tumor agent that tar-gets the energy metabolism of tumor cells. (C) 2020 Elsevier B.V. All rights reserved.