Dietary protein restriction inhibits tumor growth in human xenograft models of prostate and breast cancer

Fontana, Luigi; Adelaiye, Remi; Rastelli, Antonella; Miles, Kiersten Marie; Ciamporcero, Eric; Longo, Valter D.; Nguyen, Holly M.; Vessella, Robert L.; Пили, Роберто

doi:10.18632/oncotarget.1586

Cited by 108 publications

(104 citation statements)

References 32 publications

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“…This system is activated by insulin and other growth factors through the kinases PI3K and AKT and it is inhibited by AMP-activated protein kinase (AMPK), a key sensor of energy status activated in response to low ATP levels. Conversely, the down-regulation of the insulin pathway and the overexpression of AMPK lead to mTORC1 inhibition that has been linked to stress resistance and to a reduced chronic age-associated inflammation through the nuclear factor (NF)-κB pathway (triggered by the activation of a protein complex that controls DNA transcription) [22,24] involved in immune-inflammatory responses [25]. …”

Section: Biology Of Ageing and Longevitymentioning

confidence: 99%

Mediterranean Diet and Healthy Ageing: A Sicilian Perspective

Vasto

Buscemi²,

Barera³

et al. 2014

Gerontology

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Traditional Mediterranean diet (MedDiet) is a common dietary pattern characterizing a lifestyle and culture proven to contribute to better health and quality of life in Mediterranean countries. By analyzing the diet of centenarians from the Sicani Mountains and eating habits of inhabitants of Palermo, it is reported that a close adherence to MedDiet is observed in the countryside, whereas in big towns this adherence is not so close. This has an effect on the rates of mortality at old age (and reciprocally longevity) that are lower in the countryside than in big towns. Concerning the health effects of the diet, the low content of animal protein and the low glycaemic index of the Sicilian MedDiet might directly modulate the insulin/IGF-1 and the mTOR pathways, known to be involved in ageing and longevity. In particular, the reduction of animal protein intake may significantly reduce serum IGF-1 concentrations and inhibit mTOR activity with a down-regulation of the signal that leads to the activation of FOXO3A and, consequently, to the transcription of homeostatic genes that favour longevity. The down-regulation of both IGF-1 and mTORC1 also induces an anti-inflammatory effect. In addition to the effects on sensing pathways, many single components of MedDiet are known to have positive effects on health, reducing inflammation, optimizing cholesterol and other important risk factors of age-related diseases. However, a key role is played by polyphenols represented in high amount in the Sicilian MedDiet (in particular in extra virgin olive oil) that can work as hormetins that provide an environmental chemical signature regulating stress resistance pathways such as nuclear factor erythroid 2-related factor 2.

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Section: Biology Of Ageing and Longevitymentioning

confidence: 99%

Mediterranean Diet and Healthy Ageing: A Sicilian Perspective

Vasto

Buscemi²,

Barera³

et al. 2014

Gerontology

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“…This inhibitory effect was associated with a reduction in serum PSA and IGF-1 levels, and a down-regulation of intra-tumor mTOR activity in the LuCaP23.1 and LuCaP35V models. Protein restriction was also associated with modulation of specific histone markers suggesting epigenetic modulation (Fontana et al, 2013).…”

Section: Arginine and Protein Modified Dietmentioning

confidence: 98%

“…Fontana et al (2013) examined the effects of isocaloric modifications in dietary protein quantity or quality on tumor growth in the human xenograft LuCaP23.1, LuCaP35V prostate cancer models and WHIM16 breast cancer models. Results showed a 70% inhibition of tumor growth in the castrate-resistant LuCaP23.1 prostate cancer model and a 56% inhibition in the WHIM16 breast cancer model fed with a 7% protein diet when compared to an isocaloric 21% protein diet.…”

Section: Arginine and Protein Modified Dietmentioning

confidence: 99%

Arginine enzymatic deprivation and diet restriction for cancer treatment

Zam

2017

Braz. J. Pharm. Sci.

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Recent findings in amino acid metabolism and the differences between normal, healthy cells and neoplastic cells have revealed that targeting single amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. Arginine is derived from dietary protein intake, body protein breakdown, or endogenous de novo arginine production and several studies have revealed disturbances in its synthesis and metabolism which could enhance or inhibit tumor cell growth. Consequently, there has been an increased interest in the arginine-depleting enzymes and dietary deprivation of arginine and its precursors as a potential antineoplastic therapy. This review outlines the most recent advances in targeting arginine metabolic pathways in cancer therapy and the different chemo-and radio-therapeutic approaches to be co-applied.

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“…Similar results have been reported in human studies, showing that a long-term intake of an LP diet is associated with inhibiting the IGF/AKT/mTOR pathway and with epigenetic modifications that are linked to an increase risk of cancer. 25 To learn more about the possible factors that might influence these findings, we identified VOCs in the urine of mice maintained on HP and LP diets in their healthy, early, and late stages of the malignancy. Both type of diet and the stage of malignancy noticeably influenced the composition of the VOCs in the urine.…”

Section: Breast Cancer-effect Of Dietmentioning

confidence: 99%

Urine volatile organic compounds composition in mice bearing breast and melanoma tumors: effect of low-protein diet

Gopas¹,

Qader²,

Isaacson³

et al. 2018

CBF

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Background: Volatile organic compounds (VOCs) in urine may provide information about biomarkers of tumors in their early stages and about tumor growth. Methods: This study demonstrates that the effect of low protein diet on the pattern of VOCs in the urine of healthy and cancer bearing mice is significant. Results: Pentanal, found in nine out of the ten breast cancer-bearing mice on a high protein (HP) diet, was not found in any of the cancer bearing mice under a low protein (LP) diet, even after tumor development. In addition, the concentration of 3-heptanone, also elevated in the HP group, was not found in the LP group. Benzoic acid, 4-ethoxy-, ethyl ester, 2-pentanone, and propane, 1-isothiocyanato-3-(methylthio), all associated with anti-cancer properties or activity, were observed in the LP group, but not in the HP group. 6-methyl-3-heptanone exhibited a marked increase in concentration as a function of tumor growth when mice were maintained on an HP diet; however, its concentration exhibited no change in mice on the LP diet. The LP group showed much better survival, and even spontaneous recovery from cancer. Conclusion: Our results give an insight into the effects of an LP diet on the management of breast cancer and melanoma. While other research groups focus on improving the relative rates of efficacy and accuracy of cancer biopsy results, this study attempted to monitor the initial appearance of cancer by VOCs excreted in urine that may be associated with metabolic and other physiological changes associated with tumor development, and with a diet that inhibits such development.

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Dietary protein restriction inhibits tumor growth in human xenograft models of prostate and breast cancer

Cited by 108 publications

References 32 publications

Mediterranean Diet and Healthy Ageing: A Sicilian Perspective

Mediterranean Diet and Healthy Ageing: A Sicilian Perspective

Arginine enzymatic deprivation and diet restriction for cancer treatment

Urine volatile organic compounds composition in mice bearing breast and melanoma tumors: effect of low-protein diet

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