title: Dietary protein restriction inhibits tumor growth in human xenograft models.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Medicine, Washington University in St. Louis, MO, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
authors.forename: Remi M
authors.initials: RM
authors.lastname: Adelaiye
authors.forename: Antonella L
authors.initials: AL
authors.lastname: Rastelli
authors.forename: Kiersten Marie
authors.initials: KM
authors.lastname: Miles
authors.forename: Eric
authors.initials: E
authors.lastname: Ciamporcero
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
authors.forename: Holly
authors.initials: H
authors.lastname: Nguyen
authors.forename: Robert
authors.initials: R
authors.lastname: Vessella
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D018753:Diet, Protein-Restricted / Q000379:methods*; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D010940:Plant Proteins / Q000008:administration & dosage; D064129:Prostatic Neoplasms, Castration-Resistant / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D004044:Dietary Proteins; D010940:Plant Proteins; D007334:Insulin-Like Growth Factor I