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Nutrients, such as amino acids (<jats:styled-content style=\"fixed-case\">AA<\/jats:styled-content>s), are not only a caloric source, but can also modulate cell metabolism and modify hormone homeostasis. Our hypothesis is that the environmental messages provided by <jats:styled-content style=\"fixed-case\">AA<\/jats:styled-content>s rule the dynamics of cancer cell life or death, and the alteration of the balance between essential amino acids (<jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>s) and non\u2010essential amino acids (<jats:styled-content style=\"fixed-case\">NEAA<\/jats:styled-content>s) (lower and higher than 50%, respectively) present in nutrients may represent a key instrument to alter environment\u2010dependent messages, thus mastering cancer cells destiny. In this study, two AA mixtures, one exclusively consisting of <jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>s and the other consisting of 85% <jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>s and 15% <jats:styled-content style=\"fixed-case\">NEAA<\/jats:styled-content>s, were tested to explore their effects on the viability of both normal and cancer cell lines and to clarify the molecular mechanisms involved. Both mixtures exerted a cell\u2010dependent anti\u2010proliferative, cytotoxic effect involving the inhibition of proteasome activity and the consequent activation of autophagy and apoptosis. These results, besides further validating the notion of the peculiar interdependence and extensive crosstalk between the ubiquitin\u2013proteasome system (UPS) and autophagy, indicate that variation in the ratio of <jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">NEAA<\/jats:styled-content>s can deeply influence cancer cell survival. Consequently, customization of dietary ratios among <jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">NEAA<\/jats:styled-content>s by specific AA mixtures may represent a promising anticancer strategy able to selectively induce death of cancer cells through the induction of apoptosis <jats:italic>via<\/jats:italic> both UPS inhibition and autophagy activation.<\/jats:p>","DOI":"10.1111\/febs.14081","type":"journal-article","created":{"date-parts":[[2017,4,9]],"date-time":"2017-04-09T04:44:49Z","timestamp":1491713089000},"page":"1726-1737","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Essential amino acid mixtures drive cancer cells to apoptosis through proteasome inhibition and autophagy activation"],"prefix":"10.1111","volume":"284","author":[{"given":"Laura","family":"Bonfili","sequence":"first","affiliation":[{"name":"School of Biosciences and 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