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Resveratrol worsens survival in SCID mice with prostate cancer xenografts in a cell-line specific manner, through paradoxical effects on oncogenic pathways.

Publication ,  Journal Article
Klink, JC; Tewari, AK; Masko, EM; Antonelli, J; Febbo, PG; Cohen, P; Dewhirst, MW; Pizzo, SV; Freedland, SJ
Published in: Prostate
May 2013

BACKGROUND: Resveratrol increases lifespan and decreases the risk of many cancers. We hypothesized resveratrol will slow the growth of human prostate cancer xenografts. METHODS: SCID mice were fed Western diet (40% fat, 44% carbohydrate, 16% protein by kcal). One week later, human prostate cancer cells, either LAPC-4 (151 mice) or LNCaP (94 mice) were injected subcutaneously. Three weeks after injection, LAPC-4 mice were randomized to Western diet (control group), Western diet plus resveratrol 50 mg/kg/day, or Western diet plus resveratrol 100 mg/kg/day. The LNCaP mice were randomized to Western diet or Western diet plus resveratrol 50 mg/kg/day. Mice were sacrificed when tumors reached 1,000 mm(3). Survival differences among groups were assessed using Cox proportional hazards. Serum insulin and IGF axis were assessed using ELISAs. Gene expression was analyzed using Affymetrix gene arrays. RESULTS: Compared to control in the LAPC-4 study, resveratrol was associated with decreased survival (50 mg/kg/day--HR 1.53, P = 0.04; 100 mg/kg/day--HR 1.22, P = 0.32). In the LNCaP study, resveratrol did not change survival (HR 0.77, P = 0.22). In combined analysis of both resveratrol 50 mg/kg/day groups, IGF-1 was decreased (P = 0.05) and IGFBP-2 was increased (P = 0.01). Resveratrol induced different patterns of gene expression changes in each xenograft model, with upregulation of oncogenic pathways E2F3 and beta-catenin in LAPC-4 tumors. CONCLUSION: Resveratrol was associated with significantly worse survival with LAPC-4 tumors, but unchanged survival with LNCaP. Based on these preliminary data that resveratrol may be harmful, caution should be advised in using resveratrol for patients until further studies can be conducted.

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Published In

Prostate

DOI

EISSN

1097-0045

Publication Date

May 2013

Volume

73

Issue

7

Start / End Page

754 / 762

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Survival Analysis
  • Stilbenes
  • Resveratrol
  • Prostatic Neoplasms
  • Proportional Hazards Models
  • Oncology & Carcinogenesis
  • Mice, SCID
  • Mice
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Klink, J. C., Tewari, A. K., Masko, E. M., Antonelli, J., Febbo, P. G., Cohen, P., … Freedland, S. J. (2013). Resveratrol worsens survival in SCID mice with prostate cancer xenografts in a cell-line specific manner, through paradoxical effects on oncogenic pathways. Prostate, 73(7), 754–762. https://doi.org/10.1002/pros.22619
Klink, Joseph C., Alok K. Tewari, Elizabeth M. Masko, Jodi Antonelli, Phillip G. Febbo, Pinchas Cohen, Mark W. Dewhirst, Salvatore V. Pizzo, and Stephen J. Freedland. “Resveratrol worsens survival in SCID mice with prostate cancer xenografts in a cell-line specific manner, through paradoxical effects on oncogenic pathways.Prostate 73, no. 7 (May 2013): 754–62. https://doi.org/10.1002/pros.22619.
Klink JC, Tewari AK, Masko EM, Antonelli J, Febbo PG, Cohen P, et al. Resveratrol worsens survival in SCID mice with prostate cancer xenografts in a cell-line specific manner, through paradoxical effects on oncogenic pathways. Prostate. 2013 May;73(7):754–62.
Klink, Joseph C., et al. “Resveratrol worsens survival in SCID mice with prostate cancer xenografts in a cell-line specific manner, through paradoxical effects on oncogenic pathways.Prostate, vol. 73, no. 7, May 2013, pp. 754–62. Pubmed, doi:10.1002/pros.22619.
Klink JC, Tewari AK, Masko EM, Antonelli J, Febbo PG, Cohen P, Dewhirst MW, Pizzo SV, Freedland SJ. Resveratrol worsens survival in SCID mice with prostate cancer xenografts in a cell-line specific manner, through paradoxical effects on oncogenic pathways. Prostate. 2013 May;73(7):754–762.
Journal cover image

Published In

Prostate

DOI

EISSN

1097-0045

Publication Date

May 2013

Volume

73

Issue

7

Start / End Page

754 / 762

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Survival Analysis
  • Stilbenes
  • Resveratrol
  • Prostatic Neoplasms
  • Proportional Hazards Models
  • Oncology & Carcinogenesis
  • Mice, SCID
  • Mice
  • Male