The effect of carbohydrate restriction on prostate cancer tumor growth in a castrate mouse xenograft model

Jorge Caso, Elizabeth M. Masko, Jean A Thomas Ii, Susan H. Poulton, Mark Dewhirst, Salvatore V. Pizzo, Stephen J. Freedland

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

BACKGROUND No- and low-carbohydrate diets delay tumor growth compared to western diet (WD) in prostate cancer (PCa) xenograft studies. The effect of these diets in concert with androgen deprivation is unknown. METHODS A total of 160 male SCID mice were injected with 1× 105 LAPC-4 human PCa cells. Of these, 150 mice were castrated and randomized to an ad libitum WD or fed via a paired-feeding protocol with a no-carbohydrate ketogenic diet (NCKD), 10% carbohydrate diet, or 20% carbohydrate diet. The remaining 10 mice were not castrated and were fed an ad libitum WD. The mice were sacrificed once volumes reached 1,000 mm3 and survival tested using the log-rank test. Serum from the median surviving 8 mice/group was assayed for insulin, IGF-1, and IGFBP-3. RESULTS Body weights were roughly equal among groups. The 10 non-castrated mice experienced accelerated tumor growth. Among castrated mice, WD had the most rapid tumor growth; 20% carbohydrate diet the slowest (P = 0.046). Survival was not significantly different among the various carbohydrate restricted groups (P = 0.51). When pooled, there was a non-significant trend (P = 0.11) in improved survival among the carbohydrate restricted diets versus WD. No significant difference in serum insulin, IGF-1, and IGFBP-3 levels was noted among all groups at pre-randomization or at sacrifice. CONCLUSIONS A 20% carbohydrate diet slowed tumor growth versus a WD. Though the benefit of carbohydrate restriction was somewhat less than in prior studies in non-castrate mice, these data still suggest diets achievable in humans may play a role in PCa management.

Original languageEnglish
Pages (from-to)449-454
Number of pages6
JournalProstate
Volume73
Issue number5
DOIs
StatePublished - Apr 1 2013

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Heterografts
Prostatic Neoplasms
Carbohydrates
Diet
Growth
Neoplasms
Carbohydrate-Restricted Diet
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor I
Survival
Ketogenic Diet
Insulin
SCID Mice
Random Allocation
Serum
Androgens
Western Diet
Body Weight

Keywords

  • castration
  • diet
  • IGF-1
  • insulin
  • low-carbohydrate
  • prostate cancer

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Caso, J., Masko, E. M., Ii, J. A. T., Poulton, S. H., Dewhirst, M., Pizzo, S. V., & Freedland, S. J. (2013). The effect of carbohydrate restriction on prostate cancer tumor growth in a castrate mouse xenograft model. Prostate, 73(5), 449-454. https://doi.org/10.1002/pros.22586

The effect of carbohydrate restriction on prostate cancer tumor growth in a castrate mouse xenograft model. / Caso, Jorge; Masko, Elizabeth M.; Ii, Jean A Thomas; Poulton, Susan H.; Dewhirst, Mark; Pizzo, Salvatore V.; Freedland, Stephen J.

In: Prostate, Vol. 73, No. 5, 01.04.2013, p. 449-454.

Research output: Contribution to journalArticle

Caso, J, Masko, EM, Ii, JAT, Poulton, SH, Dewhirst, M, Pizzo, SV & Freedland, SJ 2013, 'The effect of carbohydrate restriction on prostate cancer tumor growth in a castrate mouse xenograft model', Prostate, vol. 73, no. 5, pp. 449-454. https://doi.org/10.1002/pros.22586
Caso, Jorge ; Masko, Elizabeth M. ; Ii, Jean A Thomas ; Poulton, Susan H. ; Dewhirst, Mark ; Pizzo, Salvatore V. ; Freedland, Stephen J. / The effect of carbohydrate restriction on prostate cancer tumor growth in a castrate mouse xenograft model. In: Prostate. 2013 ; Vol. 73, No. 5. pp. 449-454.
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abstract = "BACKGROUND No- and low-carbohydrate diets delay tumor growth compared to western diet (WD) in prostate cancer (PCa) xenograft studies. The effect of these diets in concert with androgen deprivation is unknown. METHODS A total of 160 male SCID mice were injected with 1× 105 LAPC-4 human PCa cells. Of these, 150 mice were castrated and randomized to an ad libitum WD or fed via a paired-feeding protocol with a no-carbohydrate ketogenic diet (NCKD), 10{\%} carbohydrate diet, or 20{\%} carbohydrate diet. The remaining 10 mice were not castrated and were fed an ad libitum WD. The mice were sacrificed once volumes reached 1,000 mm3 and survival tested using the log-rank test. Serum from the median surviving 8 mice/group was assayed for insulin, IGF-1, and IGFBP-3. RESULTS Body weights were roughly equal among groups. The 10 non-castrated mice experienced accelerated tumor growth. Among castrated mice, WD had the most rapid tumor growth; 20{\%} carbohydrate diet the slowest (P = 0.046). Survival was not significantly different among the various carbohydrate restricted groups (P = 0.51). When pooled, there was a non-significant trend (P = 0.11) in improved survival among the carbohydrate restricted diets versus WD. No significant difference in serum insulin, IGF-1, and IGFBP-3 levels was noted among all groups at pre-randomization or at sacrifice. CONCLUSIONS A 20{\%} carbohydrate diet slowed tumor growth versus a WD. Though the benefit of carbohydrate restriction was somewhat less than in prior studies in non-castrate mice, these data still suggest diets achievable in humans may play a role in PCa management.",
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AU - Masko, Elizabeth M.

AU - Ii, Jean A Thomas

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AU - Dewhirst, Mark

AU - Pizzo, Salvatore V.

AU - Freedland, Stephen J.

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N2 - BACKGROUND No- and low-carbohydrate diets delay tumor growth compared to western diet (WD) in prostate cancer (PCa) xenograft studies. The effect of these diets in concert with androgen deprivation is unknown. METHODS A total of 160 male SCID mice were injected with 1× 105 LAPC-4 human PCa cells. Of these, 150 mice were castrated and randomized to an ad libitum WD or fed via a paired-feeding protocol with a no-carbohydrate ketogenic diet (NCKD), 10% carbohydrate diet, or 20% carbohydrate diet. The remaining 10 mice were not castrated and were fed an ad libitum WD. The mice were sacrificed once volumes reached 1,000 mm3 and survival tested using the log-rank test. Serum from the median surviving 8 mice/group was assayed for insulin, IGF-1, and IGFBP-3. RESULTS Body weights were roughly equal among groups. The 10 non-castrated mice experienced accelerated tumor growth. Among castrated mice, WD had the most rapid tumor growth; 20% carbohydrate diet the slowest (P = 0.046). Survival was not significantly different among the various carbohydrate restricted groups (P = 0.51). When pooled, there was a non-significant trend (P = 0.11) in improved survival among the carbohydrate restricted diets versus WD. No significant difference in serum insulin, IGF-1, and IGFBP-3 levels was noted among all groups at pre-randomization or at sacrifice. CONCLUSIONS A 20% carbohydrate diet slowed tumor growth versus a WD. Though the benefit of carbohydrate restriction was somewhat less than in prior studies in non-castrate mice, these data still suggest diets achievable in humans may play a role in PCa management.

AB - BACKGROUND No- and low-carbohydrate diets delay tumor growth compared to western diet (WD) in prostate cancer (PCa) xenograft studies. The effect of these diets in concert with androgen deprivation is unknown. METHODS A total of 160 male SCID mice were injected with 1× 105 LAPC-4 human PCa cells. Of these, 150 mice were castrated and randomized to an ad libitum WD or fed via a paired-feeding protocol with a no-carbohydrate ketogenic diet (NCKD), 10% carbohydrate diet, or 20% carbohydrate diet. The remaining 10 mice were not castrated and were fed an ad libitum WD. The mice were sacrificed once volumes reached 1,000 mm3 and survival tested using the log-rank test. Serum from the median surviving 8 mice/group was assayed for insulin, IGF-1, and IGFBP-3. RESULTS Body weights were roughly equal among groups. The 10 non-castrated mice experienced accelerated tumor growth. Among castrated mice, WD had the most rapid tumor growth; 20% carbohydrate diet the slowest (P = 0.046). Survival was not significantly different among the various carbohydrate restricted groups (P = 0.51). When pooled, there was a non-significant trend (P = 0.11) in improved survival among the carbohydrate restricted diets versus WD. No significant difference in serum insulin, IGF-1, and IGFBP-3 levels was noted among all groups at pre-randomization or at sacrifice. CONCLUSIONS A 20% carbohydrate diet slowed tumor growth versus a WD. Though the benefit of carbohydrate restriction was somewhat less than in prior studies in non-castrate mice, these data still suggest diets achievable in humans may play a role in PCa management.

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KW - diet

KW - IGF-1

KW - insulin

KW - low-carbohydrate

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