Nutrition, Nitrogen Requirements, Exercise and Chemotherapy-Induced Toxicity in Cancer Patients. A puzzle of Contrasting Truths?

Flati, Vincenzo; Corsetti, Giovanni; Pasini, Evasio; Rufo, Anna; Romano, Claudia; Dioguardi, Francesco Saverio

doi:10.2174/1871520615666150824152900

Cited by 8 publications

(15 citation statements)

References 130 publications

(147 reference statements)

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“…The relation between nutrition and cancer is an unresolved question with many possible answers since even cancer cells' peculiar energy production from glucose is still debated [29]. Nutrients in the diet may influence cancer development [3,6,16,18,28]. Supplementation with balanced formulations of EAAs exerted positive effects in the prevention of several human pathologies, in the improvement of the quality of life, in reducing oxidative damage and in increasing average life span in mice [3,6,13,14,16,17].…”

Section: Discussionmentioning

confidence: 99%

“…Nutrients in the diet may influence cancer development [3,6,16,18,28]. Supplementation with balanced formulations of EAAs exerted positive effects in the prevention of several human pathologies, in the improvement of the quality of life, in reducing oxidative damage and in increasing average life span in mice [3,6,13,14,16,17]. While AAs are indispensable for cells life, AA-induced cytotoxicity is documented in cancer cells, but few data are available on the molecular mechanisms involved [6,19,30].…”

Section: Discussionmentioning

confidence: 99%

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Essential amino acid mixtures drive cancer cells to apoptosis through proteasome inhibition and autophagy activation

et al. 2017

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Essential amino acid mixtures drive cancer cells to apoptosis through proteasome inhibition and autophagy activation

et al. 2017

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“…The apparent discrepancy between pro-disease and anti-disease activity of mTOR in the lung may be explained by the multiple activities exerted by mTOR through multi-protein complexes (TORC1 and TORC2) which may work synergistically, independently or antagonistically. Both complexes are influenced by internal and external cell stimuli (2,3). Thus, the contradictory results obtained by using mTOR inhibitors and nowadays presented in the scientific literature are probably context-dependent and possibly influenced by many factors such as the species tested, the experimental model, age and animals used, the presence of concomitant diseases, the genotype/phenotype of lung disease studied, etc.…”

Section: Mtor Targeting In Lung Diseasesmentioning

confidence: 99%

“…It plays an important role in regulating fundamental metabolic processes such as inflammation, autophagy, apoptosis, proteins synthesis and/or cytoskeleton organization which influence cell's survival or death, by integrating internal and external cell stimuli (1). mTOR is a highly conserved serinethreonine kinase (1), which belongs to the phosphoinositide 3-kinase-related protein kinase family, PIKK (2)(3)(4). It is found in two distinct protein kinase complexes: mTORC1 and mTORC2.…”

Section: Introductionmentioning

confidence: 99%

“…It is found in two distinct protein kinase complexes: mTORC1 and mTORC2. They can act either synergistically, independently or even antagonistically, according to the prevalence of the various stimuli (2,3). Both mTORC1 and mTORC2 complexes have common subunits, i.e., mTOR catalytic subunit and mLST8 (also known as GbL), whereas other components distinguish them.…”

Section: Introductionmentioning

confidence: 99%

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Mammalian Target of Rapamycin: Is It Relevant to COPD Pathogenesis or Treatment?

Pasini

Flati

Comini

et al. 2019

COPD: Journal of Chronic Obstructive Pulmonary Disease

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The mammalian target of rapamycin (mTOR) signalling pathway regulates fundamental metabolic processes such as inflammation, autophagy and apoptosis, all of which influence cell fate. Recent experimental data suggest that mTOR signalling is involved in many diseases, including lung diseases, but with contrasting data. Overexpression of mTOR and its signalling proteins have been linked to lung cell senescence and development of emphysema, pulmonary hypertension and inflammation. On the other hand, mTOR inhibitors, as rapamycin and/or its derivatives, restore corticosteroid sensitivity in peripheral blood mononuclear cells from chronic obstructive pulmonary disease (COPD) patients, and overexpression of mTOR suppresses cigarette smoke-induced inflammation and emphysema, suggesting that induction of mTOR expression/activity might be useful to treat COPD. This apparent discrepancy is due to complex and heterogenic enzymatic pathway of mTOR. Translation of pre-clinical positive data on the use of mTOR inhibitors to COPD therapy needs a more in-depth knowledge of mTOR signalling. ARTICLE HISTORY

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Is the Response of Tumours Dependent on Dietary Input of Some Amino Acids or on the Ratios Among Essential and Non-Essential Amino Acids? All That Glisters is Not Gold

Dioguardi¹,

Flati²,

Corsetti³

et al. 2018

Preprint

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Production of energy is a main task of cancer cells metabolism, since costs of duplicating are enormous. Although energy is derived in cells by dismantling carbon to carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as dependent on glycolysis. Since the end of the last century, awareness of dependence of cancer metabolism on amino acids not only for protein syntheses but also for matching energy needs has grown. The roles of specific amino acids, like glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, there are epidemiological evidences that some amino acids used as supplement for therapeutic reasons (the branched chain ones) may reduce incidence of liver cancer, and some molecular mechanism has been proposed as functional to their protective action. On the contrary, metabolic signature of some pathology connected with increased risk of cancer, like prolonged hyperinsulinemia in insulin resistant patients, is signed by plasma elevated levels of the same branched chain amino acids, posing puzzling questions to clinicians. Most recently, peculiar formulations of amino acids, deeply different if compared to amino acids compositions normally present in foods, have shown the power to master epigenetics slowing growth or driving cancer cells to apoptotic death, while being even beneficial for normal cells and for animals health and life span. In this review, we will analyze and try to disentangle some of the many knots dealing with complexities of amino acids biology and linked to cancer metabolism.

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Nutrition, Nitrogen Requirements, Exercise and Chemotherapy-Induced Toxicity in Cancer Patients. A puzzle of Contrasting Truths?

Cited by 8 publications

References 130 publications

Essential amino acid mixtures drive cancer cells to apoptosis through proteasome inhibition and autophagy activation

Essential amino acid mixtures drive cancer cells to apoptosis through proteasome inhibition and autophagy activation

Mammalian Target of Rapamycin: Is It Relevant to COPD Pathogenesis or Treatment?

Is the Response of Tumours Dependent on Dietary Input of Some Amino Acids or on the Ratios Among Essential and Non-Essential Amino Acids? All That Glisters is Not Gold

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