Corsetti Giovanni, Romano Claudia, Codenotti Silvia, Pasini Evasio, Fanzani Alessandro, Scarabelli Tiziano, Dioguardi Francesco S
Department of Clinical and Experimental Sciences, University of Brescia, 25121 Brescia, Italy.
Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy.
Int J Mol Sci. 2025 Jul 21;26(14):7014. doi: 10.3390/ijms26147014.
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.
肿瘤细胞的代谢亢进需要大量能量和分子来构建新细胞并使肿瘤扩张,从而将这些资源从健康细胞中转移。氨基酸(AAs)是蛋白质构建中唯一具有全能性且必不可少的分子。先前在人类和小鼠癌细胞中的体外研究以及在小鼠中的体内研究表明,过量的必需氨基酸(EAAs)通过促进细胞凋亡和自噬对肿瘤增殖产生抑制作用。在本研究中,我们在体外和体内评估了基于EAA的混合物是否会影响人结肠癌(HCT116)的发展。为此,在体外,我们评估了用特殊EAA混合物处理的HCT116细胞的增殖情况。在体内,将皮下(s.c.)或腹腔内(i.p.)注射HCT116细胞的免疫抑制无胸腺裸鼠与标准实验室饮食(StD)相比,给予改良的富含EAA的饮食(EAARD)。体外数据表明,EAA混合物通过诱导细胞凋亡和自噬来损害癌症生长。在体内,结果表明,喂食EAARD的小鼠形成的皮下肿瘤明显小于喂食StD的小鼠(总质量分别为3.24 g和6.09 g)。腹腔注射并喂食EAARD的小鼠比喂食StD的小鼠腹腔内肿瘤更小且数量更少(总质量分别为0.79 g和4.77 g)。EAAs通过诱导自噬和细胞凋亡、增加内质网应激以及抑制炎症和新血管形成来阻止HCT116细胞的生长。此外,喂食EAARD的小鼠维持了肌肉质量以及白色和棕色脂肪组织。富含EAAs的饮食会影响人结肠癌细胞的存活和增殖能力,同时在肌肉细胞中维持合成代谢刺激。