title: A low carbohydrate, high protein diet suppresses intratumoral androgen synthesis and slows castration-resistant prostate tumor growth in mice.
abstract: Dietary factors continue to preside as dominant influences in prostate cancer prevalence and progression-free survival following primary treatment. We investigated the influence of a low carbohydrate diet, compared to a typical Western diet, on prostate cancer (PCa) tumor growth in vivo. LNCaP xenograft tumor growth was studied in both intact and castrated mice, representing a more advanced castration resistant PCa (CRPC). No differences in LNCaP tumor progression (total tumor volume) with diet was observed for intact mice (P = 0.471) however, castrated mice on the Low Carb diet saw a statistically significant reduction in tumor growth rate compared with Western diet fed mice (P = 0.017). No correlation with serum PSA was observed. Steroid profiles, alongside serum cholesterol and cholesteryl ester levels, were significantly altered by both diet and castration. Specifically, DHT concentration with the Low Carb diet was 58% that of the CRPC-bearing mice on the Western diet. Enzymes in the steroidogenesis pathway were directly impacted and tumors isolated from intact mice on the Low Carb diet had higher AKR1C3 protein levels and lower HSD17B2 protein levels than intact mice on the Western diet (ARK1C3: P = 0.074; HSD17B2: P = 0.091, with α = 0.1). In contrast, CRPC tumors from mice on Low Carb diets had higher concentrations of both HSD17B2 (P = 0.016) and SRD5A1 (P = 0.058 with α = 0.1) enzymes. There was no correlation between tumor growth in castrated mice for Low Carb diet versus Western diet and (a) serum insulin (b) GH serum levels (c) insulin receptor (IR) or (d) IGF-1R in tumor tissue. Intact mice fed Western diet had higher serum insulin which was associated with significantly higher blood glucose and tumor tissue IR. We conclude that both diet and castration have a significant impact on the endocrinology of mice bearing LNCaP xenograft tumors. The observed effects of diet on cholesterol and steroid regulation impact tumor tissue DHT specifically and are likely to be mechanistic drivers behind the observed tumor growth suppression.
authors: Vancouver Prostate Centre, Vancouver, British Columbia, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia V6H-3Z6, Canada; Department of Psychology, University of British Columbia, Vancouver, British Columbia V6T-1Z4, Canada.
authors: H Bobby
authors: HB
authors: Fokidis
authors: Vancouver Prostate Centre, Vancouver, British Columbia, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia V6H-3Z6, Canada.
authors: Mei
authors: M
authors: Yieng Chin
authors: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z-1L3, Canada.
authors: Victor W
authors: VW
authors: Ho
authors: Vancouver Prostate Centre, Vancouver, British Columbia, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia V6H-3Z6, Canada.
authors: Hans H
authors: HH
authors: Adomat
authors: Department of Psychology, University of British Columbia, Vancouver, British Columbia V6T-1Z4, Canada.
authors: Kiran K
authors: KK
authors: Soma
authors: Vancouver Prostate Centre, Vancouver, British Columbia, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia V6H-3Z6, Canada.
authors: Ladan
authors: L
authors: Fazli
authors: Vancouver Prostate Centre, Vancouver, British Columbia, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia V6H-3Z6, Canada.
authors: Ka Mun
authors: KM
authors: Nip
authors: Vancouver Prostate Centre, Vancouver, British Columbia, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia V6H-3Z6, Canada.
authors: Michael
authors: M
authors: Cox
authors: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z-1L3, Canada.
authors: Gerald
authors: G
authors: Krystal
authors: Vancouver Prostate Centre, Vancouver, British Columbia, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia V6H-3Z6, Canada.
authors: Amina
authors: A
authors: Zoubeidi
authors: Vancouver Prostate Centre, Vancouver, British Columbia, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia V6H-3Z6, Canada. Electronic address: eguns@prostatecentre.com.
authors: Emma S
authors: ES
authors: Tomlinson Guns
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000074425:Aldo-Keto Reductase Family 1 Member C3; D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002369:Castration; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D050528:Diet, Carbohydrate-Restricted; D066273:Diet, Western; D004044:Dietary Proteins / Q000008:administration & dosage*; D004960:Estradiol Dehydrogenases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000728:Androgens; D001786:Blood Glucose; D002788:Cholesterol Esters; D004044:Dietary Proteins; D007328:Insulin; D008565:Membrane Proteins; D013006:Growth Hormone; D002784:Cholesterol; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3; D004960:Estradiol Dehydrogenases; C523763:HSD17B2 protein, human; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548467:SRD5A1 protein, human; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D017430:Prostate-Specific Antigen
keywords: CRPC; Intratumoral androgens; Low carbohydrate high protein diet; Prostate cancer; Steroidogenesis