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 pro
tein 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 in
fluence the development of human colon cancer (HCT116). To this end, in vitro, we as
sessed the proliferation of HCT116 cells treated with a special mix of EAA. In vivo, im
munosuppressed 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 inflam
mation 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.