scholarly journals Per- and Polyfluoroalkyl Substance Exposure Combined with High-Fat Diet Supports Prostate Cancer Progression

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3902
Author(s):  
Ozan Berk Imir ◽  
Alanna Zoe Kaminsky ◽  
Qian-Ying Zuo ◽  
Yu-Jeh Liu ◽  
Ratnakar Singh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
High Fat Diet ◽  
Flame Retardants ◽  
Epidemiological Studies ◽  
Cancer Development ◽  
Prostate Cancer Progression ◽  
High Fat ◽  
The Impact

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals utilized in various industrial settings and include products such as flame retardants, artificial film-forming foams, cosmetics, and non-stick cookware, among others. Epidemiological studies suggest a link between increased blood PFAS levels and prostate cancer incidence, but the mechanism through which PFAS impact cancer development is unclear. To investigate the link between PFAS and prostate cancer, we evaluated the impact of metabolic alterations resulting from a high-fat diet combined with PFAS exposure on prostate tumor progression. We evaluated in vivo prostate cancer xenograft models exposed to perfluorooctane sulfonate (PFOS), a type of PFAS compound, and different diets to study the effects of PFAS on prostate cancer progression and metabolic activity. Metabolomics and transcriptomics were used to understand the metabolic landscape shifts upon PFAS exposure. We evaluated metabolic changes in benign or tumor cells that lead to epigenomic reprogramming and altered signaling, which ultimately increase tumorigenic risk and tumor aggressiveness. Our studies are the first in the field to provide new and clinically relevant insights regarding novel metabolic and epigenetic states as well as to support the future development of effective preventative and therapeutic strategies for PFAS-induced prostate cancers. Our findings enhance understanding of how PFAS synergize with high-fat diets to contribute to prostate cancer development and establish an important basis to mitigate PFAS exposure.

scholarly journals High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
David P. Labbé ◽  
Giorgia Zadra ◽  
Meng Yang ◽  
Jaime M. Reyes ◽  
Charles Y. Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
High Fat Diet ◽  
Cellular Proliferation ◽  
Saturated Fat ◽  
Prostate Cancer Progression ◽  
Transcriptional Program ◽  
High Fat ◽  
Metabolic Alterations ◽  
Increased Risk

Abstract Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked with increased risk of prostate cancer progression and mortality, but the molecular underpinnings of this association are poorly understood. Here, we demonstrate in a murine prostate cancer model, that high-fat diet (HFD) enhances the MYC transcriptional program through metabolic alterations that favour histone H4K20 hypomethylation at the promoter regions of MYC regulated genes, leading to increased cellular proliferation and tumour burden. Saturated fat intake (SFI) is also associated with an enhanced MYC transcriptional signature in prostate cancer patients. The SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, switching from a high-fat to a low-fat diet, attenuates the MYC transcriptional program in mice. Our findings suggest that in primary prostate cancer, dietary SFI contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet.

scholarly journals MP66-13 MIR-130A MODULATES HIGH-FAT DIET-INDUCED PROSTATE CANCER PROGRESSION THROUGH THE ACTIVATION OF MET

2016 ◽  
Vol 195 (4S) ◽  
Author(s):  
Taketoshi Nara ◽  
Shintaro Narita ◽  
Huang Mingguo ◽  
Toshiaki Yoshioka ◽  
Koichiro Takayama ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
High Fat Diet ◽  
Prostate Cancer Progression ◽  
High Fat

285 PROSTATE CANCER PROGRESSION UNDER HIGH-FAT DIET IS ENHANCED BY MCP-1/CCR2 SIGNALING

2011 ◽  
Vol 185 (4S) ◽  
Author(s):  
Mingguo Huang ◽  
Shintaro Narita ◽  
Kazuyuki Numakura ◽  
Takashi Obara ◽  
Hiroshi Tsuruta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
High Fat Diet ◽  
Prostate Cancer Progression ◽  
High Fat

scholarly journals Research Evidence on High-Fat Diet-Induced Prostate Cancer Development and Progression

2019 ◽  
Vol 8 (5) ◽  
pp. 597 ◽  
Author(s):  
Shintaro Narita ◽  
Taketoshi Nara ◽  
Hiromi Sato ◽  
Atsushi Koizumi ◽  
Mingguo Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Cancer Development ◽  
Preclinical Studies ◽  
Preclinical Models ◽  
High Fat ◽  
Prostate Cancer Development ◽  
Underlying Mechanisms ◽  
The Impact

Although recent evidence has suggested that a high-fat diet (HFD) plays an important role in prostate carcinogenesis, the underlying mechanisms have largely remained unknown. This review thus summarizes previous preclinical studies that have used prostate cancer cells and animal models to assess the impact of dietary fat on prostate cancer development and progression. Large variations in the previous studies were found during the selection of preclinical models and types of dietary intervention. Subcutaneous human prostate cancer cell xenografts, such as LNCaP, LAPC-4, and PC-3 and genetic engineered mouse models, such as TRAMP and Pten knockout, were frequently used. The dietary interventions had not been standardized, and distinct variations in the phenotype were observed in different studies using distinct HFD components. The use of different dietary components in the research models is reported to influence the effect of diet-induced metabolic disorders. The proposed underlying mechanisms for HFD-induced prostate cancer were divided into (1) growth factor signaling, (2) lipid metabolism, (3) inflammation, (4) hormonal modulation, and others. A number of preclinical studies proposed that dietary fat and/or obesity enhanced prostate cancer development and progression. However, the relationship still remains controversial, and care should be taken when interpreting the results in a human context. Future studies using more sophisticated preclinical models are imperative in order to explore deeper understanding regarding the impact of dietary fat on the development and progression of prostate cancer.

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