A Diet Rich in Essential Amino Acids Inhibits the Growth of HCT116 Human Colon Cancer Cell In Vitro and In Vivo

The metabolic hyperactivity of tumor cells demands a substantial amount of energy and molecules to build new cells and expand the tumor, diverting these resources from healthy cells. Amino acids (AAs) are the only totipotent and essential molecules for protein construction. Previous in vitro studies in human and murine cancer cells, along with in vivo studies in mice, have shown that an excess of essential amino acids (EAAs) exerts an inhibitory effect on tumor proliferation by promoting apoptosis and autophagy. In this study, both in vitro and in vivo, we evaluated whether a mixture based on EAA can influence the development of human colon cancer (HCT116). To this end, in vitro, we assessed the proliferation of HCT116 cells treated with a special mix of EAA. In vivo, immunosuppressed athymic nude mice, injected with HCT116 cells subcutaneously (s.c.) or intraperitoneally (i.p.), were given a modified EAAs-rich diet (EAARD) compared to the standard laboratory diet (StD). In vitro data showed that the EAA mix impairs cancer growth by inducing apoptosis and autophagy. In vivo, the results demonstrated that EAARD-fed mice developed s.c. tumors significantly smaller than those of StD-fed mice (total mass 3.24 vs. 6.09 g, respectively). Mice injected i.p. and fed with EAARD showed a smaller and more limited number of intra-peritoneal tumors than StD-fed mice (total mass 0.79 vs. 4.77 g, respectively). EAAs prevents the growth of HCT116 cells by inducing autophagy and apoptosis, increasing endoplasmic reticulum stress, and inhibiting inflammation and neo-vascularization. In addition, the EAARD-fed mice, maintained muscle mass and white and brown adipose tissues. A diet with an excess of EAAs affects the survival and proliferative capacity of human colon cancer cells, maintaining anabolic stimuli in muscular cells.