Essential amino acid mixtures drive cancer cells to apoptosis through proteasome inhibition and autophagy activation. (11th May 2017)

• Record Type: Journal Article
• Authors: Bonfili, Laura; Cecarini, Valentina; Cuccioloni, Massimiliano; Angeletti, Mauro; Flati, Vincenzo; Corsetti, Giovanni; Pasini, Evasio; Dioguardi, Francesco S.; Eleuteri, Anna Maria
• Is Part Of: FEBS journal. Volume 284:Number 11(2017)
• Page Start: 1726
• Page End: 1737
• Publication Date: 2017-05-11
• Subjects: amino acids -- apoptosis -- autophagy -- cancer -- proteasome; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.14081
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Cancer cells require both energy and material to survive and duplicate in a competitive environment. Nutrients, such as amino acids (AAs), 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 AAs rule the dynamics of cancer cell life or death, and the alteration of the balance between essential amino acids (EAAs) and non‐essential amino acids (NEAAs) (lower and higher than 50%, respectively) present in nutrients may represent a key instrument to alter environment‐dependent messages, thus mastering cancer cells destiny. In this study, two AA mixtures, one exclusively consisting of EAAs and the other consisting of 85% EAAs and 15% NEAAs, 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‐dependent anti‐proliferative, 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–proteasome system (UPS) and autophagy, indicate that variation in the ratio of EAAs and NEAAs can deeply influence cancer cell survival. Consequently, customization of dietary ratios among EAAs and NEAAs by specific AA mixtures may represent a promising anticancer strategy able to selectively induce death of cancer cells through the induction of apoptosis via both UPS inhibition and autophagy activation. Abstract : The opportune tuning of the ratio between essential and non‐essential amino acids, within the range tolerable for normal mammals, may represent a promising anticancer strategy to selectively induce cancer cell death through the induction of apoptosis via inhibition of the ubiquitin–proteasome system and activation of autophagy.