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

Abstract

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.

Human DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis

“…Dietary fat not only promotes obesity, but also PCa progression and disease aggressiveness. Several preclinical PCa studies have compared high-fat (or Western-style diets) versus low fat diet and reported that the former promotes AKT and ERK activity, tumor growth, tumor incidence in genetically engineered/transgenic mouse models, tumor progression to CRPC and metastasis (reviewed in Narita et al, 2019 ). Clinical case-control studies indicated saturated fat is associated with an increased risk of advanced PCa ( Bairati et al, 1998 ; Stéfani et al, 2000 ; Slattery et al, 1990 ; Whittemore et al, 1995 ).…”

Astragalus Polysaccharides Inhibits Tumorigenesis and Lipid Metabolism Through miR-138-5p/SIRT1/SREBP1 Pathway in Prostate Cancer

“…Epidemiological studies suggested that a high-fat diet plays a critical role in the development of PCa (Ferro et al, 2017;Narita et al, 2019). Further findings indicated deregulated lipid metabolism was positively associated with advanced PCa.…”

Sex Steroids and Adipokines in Men With Prostate Cancer and Their Relationship With Obesity and Metabolic Syndrome

“…Z kolei czynnikami o właściwościach protekcyjnych, oprócz zwiększonej aktywności fizycznej, są spożywanie dużych ilości ryb i warzyw, zwłaszcza pomidorów [29]. Badania sugerują, że ilość tłuszczu w diecie wpływa nie tylko na rozwój, ale też na stopień agresywności raka stercza [30].…”

“…Duża prospektywna analiza wykazała, że wyższe stężenia peptydu C w surowicy były ściśle związane ze zwiększoną śmiertelnością u chorych z rakiem stercza [41], a wysoki poziom insuliny oraz aktywacja osi insulina i IGF-1/IGF-1R poprzez sygnalizację kinazy tyrozynowej zwiększały progresję raka. Pobudzenie receptorów kinazy tyrozynowej skutkuje aktywacją kaskady białek wewnątrzkomórkowych i zmianą ekspresji genów syntezy białek [30].…”