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

Ozan Berk Imir,Wen-Yang Hu,Wen-Yang Hu,Joseph Irudayaraj,Joseph Irudayaraj,Yu-Jeh Liu,Alanna Zoe Kaminsky,Zeynep Madak Erdogan,Zeynep Madak Erdogan,Zeynep Madak Erdogan,Zeynep Madak Erdogan,Zeynep Madak Erdogan,Michael J Spinella,Ratnakar Singh,Gail S Prins,Gail S Prins,Qian-Ying Zuo

doi:10.3390/nu13113902

Abstract

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.

Highlights

Per- and polyfluoroalkyl substances (PFAS) are fluorocarbons with a carbon backbone flanked with fluorine atoms and capped with a carboxyl group
When benign and prostate cancer cells were exposed to varying concentrations of PFAS
Our findings indicate that PFAS exposure increases in vitro of tumorbenign growthand in mouse

Summary

Introduction

Per- and polyfluoroalkyl substances (PFAS) are fluorocarbons with a carbon backbone flanked with fluorine atoms and capped with a carboxyl group. PFAS adhere to metal, plastic, or other charged surfaces via an electronegative carboxylic acid group and polymerize with other PFAS compounds via fluorine atoms on their long carbon chains, forming a surface coating [1,2,3,4]. PFAS do not break down these compounds are very persistent in both the environment and the human body. Due to their low manufacturing cost and wide range of uses, PFAS come in many forms. Perfluorooctane sulfonate (PFOS), perfluorobutane sulfonic acid (PFBS), and perfluorooctanoic acid (PFOA)

Methods

Results

Discussion

Conclusion