King Grub
2014-01-30, 08:46
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.
The results from our studies may have a rapid translation into the clinic. We envision that patients with recurrent PCa and BC could be offered diet modifications involving protein dietary content at different stages of their disease with appropriate monitoring. The absence of a differential effect in the AS and CR LuCaP23.1 models suggest that the androgen status does not affect the response of PCa to protein restriction. Furthermore, intratumor androgen receptor expression was not inhibited in the 7% protein diet group (data not shown). An ongoing clinical study in patients with newly diagnosed PCa will provide important information on the biological changes following this dietary intervention before prostatectomy.
In summary, a high-protein diet promoted the growth of human LuCaP23.1 and WHIM16 tumors in mice, and a reduction in protein intake resulted in a significant inhibition of tumor growth even when the diet was started after the formation of measurable tumors, possibly through inhibition of the IGF/Akt/mTOR pathway and epigenetic modifications. Moreover, our findings indicate that plant proteins partially inhibit prostate cancer growth independently of caloric or proteic intake, suggesting that protein quality plays a key role in the progression of prostate and breast cancer. Clinical studies in patients with prostate and breast cancer are warranted to confirm the impact of dietary modifications in protein content and quality on tumor progression.
Oncotarget. 2013 Dec;4(12):2451-61. Dietary protein restriction inhibits tumor growth in human xenograft models.
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=1586&path%5B%5D=1756
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.
The results from our studies may have a rapid translation into the clinic. We envision that patients with recurrent PCa and BC could be offered diet modifications involving protein dietary content at different stages of their disease with appropriate monitoring. The absence of a differential effect in the AS and CR LuCaP23.1 models suggest that the androgen status does not affect the response of PCa to protein restriction. Furthermore, intratumor androgen receptor expression was not inhibited in the 7% protein diet group (data not shown). An ongoing clinical study in patients with newly diagnosed PCa will provide important information on the biological changes following this dietary intervention before prostatectomy.
In summary, a high-protein diet promoted the growth of human LuCaP23.1 and WHIM16 tumors in mice, and a reduction in protein intake resulted in a significant inhibition of tumor growth even when the diet was started after the formation of measurable tumors, possibly through inhibition of the IGF/Akt/mTOR pathway and epigenetic modifications. Moreover, our findings indicate that plant proteins partially inhibit prostate cancer growth independently of caloric or proteic intake, suggesting that protein quality plays a key role in the progression of prostate and breast cancer. Clinical studies in patients with prostate and breast cancer are warranted to confirm the impact of dietary modifications in protein content and quality on tumor progression.
Oncotarget. 2013 Dec;4(12):2451-61. Dietary protein restriction inhibits tumor growth in human xenograft models.
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=1586&path%5B%5D=1756