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Dietary protein restriction inhibits tumor growth in human xenograft models.

Abstract

PURPOSE

Data from epidemiological and experimental studies suggest that dietary protein intake may play a role in inhibiting prostate and breast cancer by modulating the IGF/AKT/mTOR pathway. In this study we investigated the effects of diets with different protein content or quality on prostate and breast cancer.

EXPERIMENTAL DESIGN

To test our hypothesis we assessed the inhibitory effect of protein diet restriction on prostate and breast cancer growth, serum PSA and IGF-1 concentrations, mTOR activity and epigenetic markers, by using human xenograft cancer models.

RESULTS

Our 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. Inhibition of tumor growth correlated, in the LuCaP23.1 model, with decreased serum PSA and IGF-1 levels, down-regulation of mTORC1 activity, decreased cell proliferation as indicated by Ki67 staining, and reduction in epigenetic markers of prostate cancer progression, including the histone methyltransferase EZH2 and the associated histone mark H3K27me3. In addition, we observed that modifications of dietary protein quality, independently of protein quantity, decreased tumor growth. A diet containing 20% plant protein inhibited tumor weight by 37% as compared to a 20% animal dairy protein diet.

CONCLUSIONS

Our findings suggest that a reduction in dietary protein intake is highly effective in inhibiting tumor growth in human xenograft prostate and breast cancer models, possibly through the inhibition of the IGF/AKT/mTOR pathway and epigenetic modifications.

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  • Authors+Show Affiliations

    ,

    Department of Medicine, Washington University in St. Louis, MO, USA.

    , , , , , , ,

    Source

    Oncotarget 4:12 2013 Dec pg 2451-61

    MeSH

    Animals
    Apoptosis
    Breast Neoplasms
    Cell Growth Processes
    Cell Line, Tumor
    Diet, Protein-Restricted
    Dietary Proteins
    Female
    Humans
    Insulin-Like Growth Factor I
    Male
    Mice
    Mice, Inbred ICR
    Mice, SCID
    Plant Proteins
    Prostatic Neoplasms, Castration-Resistant
    Random Allocation
    Xenograft Model Antitumor Assays

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24353195

    Citation

    Fontana, Luigi, et al. "Dietary Protein Restriction Inhibits Tumor Growth in Human Xenograft Models." Oncotarget, vol. 4, no. 12, 2013, pp. 2451-61.
    Fontana L, Adelaiye RM, Rastelli AL, et al. Dietary protein restriction inhibits tumor growth in human xenograft models. Oncotarget. 2013;4(12):2451-61.
    Fontana, L., Adelaiye, R. M., Rastelli, A. L., Miles, K. M., Ciamporcero, E., Longo, V. D., ... Pili, R. (2013). Dietary protein restriction inhibits tumor growth in human xenograft models. Oncotarget, 4(12), pp. 2451-61.
    Fontana L, et al. Dietary Protein Restriction Inhibits Tumor Growth in Human Xenograft Models. Oncotarget. 2013;4(12):2451-61. PubMed PMID: 24353195.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Dietary protein restriction inhibits tumor growth in human xenograft models. AU - Fontana,Luigi, AU - Adelaiye,Remi M, AU - Rastelli,Antonella L, AU - Miles,Kiersten Marie, AU - Ciamporcero,Eric, AU - Longo,Valter D, AU - Nguyen,Holly, AU - Vessella,Robert, AU - Pili,Roberto, PY - 2013/12/20/entrez PY - 2013/12/20/pubmed PY - 2014/11/13/medline SP - 2451 EP - 61 JF - Oncotarget JO - Oncotarget VL - 4 IS - 12 N2 - PURPOSE: Data from epidemiological and experimental studies suggest that dietary protein intake may play a role in inhibiting prostate and breast cancer by modulating the IGF/AKT/mTOR pathway. In this study we investigated the effects of diets with different protein content or quality on prostate and breast cancer. EXPERIMENTAL DESIGN: To test our hypothesis we assessed the inhibitory effect of protein diet restriction on prostate and breast cancer growth, serum PSA and IGF-1 concentrations, mTOR activity and epigenetic markers, by using human xenograft cancer models. RESULTS: Our 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. Inhibition of tumor growth correlated, in the LuCaP23.1 model, with decreased serum PSA and IGF-1 levels, down-regulation of mTORC1 activity, decreased cell proliferation as indicated by Ki67 staining, and reduction in epigenetic markers of prostate cancer progression, including the histone methyltransferase EZH2 and the associated histone mark H3K27me3. In addition, we observed that modifications of dietary protein quality, independently of protein quantity, decreased tumor growth. A diet containing 20% plant protein inhibited tumor weight by 37% as compared to a 20% animal dairy protein diet. CONCLUSIONS: Our findings suggest that a reduction in dietary protein intake is highly effective in inhibiting tumor growth in human xenograft prostate and breast cancer models, possibly through the inhibition of the IGF/AKT/mTOR pathway and epigenetic modifications. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/24353195/full_citation L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=1586 DB - PRIME DP - Unbound Medicine ER -