Dose-dependent benefits of quercetin on tumorigenesis in the C3(1)/SV40Tag transgenic mouse model of breast cancer

J. L. Steiner, J. M. Davis, J. L. McClellan, R. T. Enos, James Carson, R. Fayad, M. Nagarkatti, P. S. Nagarkatti, D. Altomare, K. E. Creek, E. A. Murphy

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Abstract

Breast cancer is the leading cause of cancer related death in women. Quercetin is a flavonol shown to have anticarcinogenic actions. However, few studies have investigated the dose-dependent effects of quercetin on tumorigenesis and none have used the C3(1)/SV40 Tag breast cancer mouse model. At 4 weeks of age female C3(1)/SV40 Tag mice were randomized to one of four dietary treatments (n = 15-16/group): control (no quercetin), low-dose quercetin (0.02% diet), moderate-dose quercetin (0.2% diet), or high-dose quercetin (2% diet). Tumor number and volume was assessed twice a week and at sacrifice (20 wks). Results showed an inverted 'U' dose-dependent effect of dietary quercetin on tumor number and volume; at sacrifice the moderate dose was most effi cacious and reduced tumor number 20% and tumor volume 78% compared to control mice (C3-Con: 9.0 ± 0.9; C3-0.2%: 7.3 ± 0.9) and (C3- Con: 2061.8 ± 977.0 mm 3 ; and C3-0.2%: 462.9 ± 75.9 mm 3 ). Tumor volume at sacrifice was also reduced by the moderate dose compared to the high and low doses (C3-2%: 1163.2 ± 305.9 mm 3 ; C3-0.02%: 1401.5 ± 555.6 mm 3 ), as was tumor number (C3-2%: 10.7 ± 1.3 mm 3 ; C3-0.02%: 8.1 ± 1.1 mm 3 ). Gene expression microarray analysis performed on mammary glands from C3-Con and C3-0.2% mice determined that 31 genes were down-regulated and 9 genes were up-regulated more than 2-fold (P < 0.05) by quercetin treatment. We report the novel finding that there is a distinct dose-dependent effect of quercetin on tumor number and volume in a transgenic mouse model of human breast cancer, which is associated with a specific gene expression signature related to quercetin treatment.

Original languageEnglish (US)
Pages (from-to)1456-1467
Number of pages12
JournalCancer Biology and Therapy
Volume15
Issue number11
DOIs
StatePublished - Nov 1 2014

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Quercetin
Transgenic Mice
Carcinogenesis
Breast Neoplasms
Tumor Burden
Diet
Neoplasms
Human Mammary Glands
Microarray Analysis
Transcriptome
Genes
Gene Expression
Control Groups

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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Dose-dependent benefits of quercetin on tumorigenesis in the C3(1)/SV40Tag transgenic mouse model of breast cancer. / Steiner, J. L.; Davis, J. M.; McClellan, J. L.; Enos, R. T.; Carson, James; Fayad, R.; Nagarkatti, M.; Nagarkatti, P. S.; Altomare, D.; Creek, K. E.; Murphy, E. A.

In: Cancer Biology and Therapy, Vol. 15, No. 11, 01.11.2014, p. 1456-1467.

Research output: Contribution to journalArticle

Steiner, JL, Davis, JM, McClellan, JL, Enos, RT, Carson, J, Fayad, R, Nagarkatti, M, Nagarkatti, PS, Altomare, D, Creek, KE & Murphy, EA 2014, 'Dose-dependent benefits of quercetin on tumorigenesis in the C3(1)/SV40Tag transgenic mouse model of breast cancer', Cancer Biology and Therapy, vol. 15, no. 11, pp. 1456-1467. https://doi.org/10.4161/15384047.2014.955444
Steiner, J. L. ; Davis, J. M. ; McClellan, J. L. ; Enos, R. T. ; Carson, James ; Fayad, R. ; Nagarkatti, M. ; Nagarkatti, P. S. ; Altomare, D. ; Creek, K. E. ; Murphy, E. A. / Dose-dependent benefits of quercetin on tumorigenesis in the C3(1)/SV40Tag transgenic mouse model of breast cancer. In: Cancer Biology and Therapy. 2014 ; Vol. 15, No. 11. pp. 1456-1467.
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abstract = "Breast cancer is the leading cause of cancer related death in women. Quercetin is a flavonol shown to have anticarcinogenic actions. However, few studies have investigated the dose-dependent effects of quercetin on tumorigenesis and none have used the C3(1)/SV40 Tag breast cancer mouse model. At 4 weeks of age female C3(1)/SV40 Tag mice were randomized to one of four dietary treatments (n = 15-16/group): control (no quercetin), low-dose quercetin (0.02{\%} diet), moderate-dose quercetin (0.2{\%} diet), or high-dose quercetin (2{\%} diet). Tumor number and volume was assessed twice a week and at sacrifice (20 wks). Results showed an inverted 'U' dose-dependent effect of dietary quercetin on tumor number and volume; at sacrifice the moderate dose was most effi cacious and reduced tumor number 20{\%} and tumor volume 78{\%} compared to control mice (C3-Con: 9.0 ± 0.9; C3-0.2{\%}: 7.3 ± 0.9) and (C3- Con: 2061.8 ± 977.0 mm 3 ; and C3-0.2{\%}: 462.9 ± 75.9 mm 3 ). Tumor volume at sacrifice was also reduced by the moderate dose compared to the high and low doses (C3-2{\%}: 1163.2 ± 305.9 mm 3 ; C3-0.02{\%}: 1401.5 ± 555.6 mm 3 ), as was tumor number (C3-2{\%}: 10.7 ± 1.3 mm 3 ; C3-0.02{\%}: 8.1 ± 1.1 mm 3 ). Gene expression microarray analysis performed on mammary glands from C3-Con and C3-0.2{\%} mice determined that 31 genes were down-regulated and 9 genes were up-regulated more than 2-fold (P < 0.05) by quercetin treatment. We report the novel finding that there is a distinct dose-dependent effect of quercetin on tumor number and volume in a transgenic mouse model of human breast cancer, which is associated with a specific gene expression signature related to quercetin treatment.",
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AU - Carson, James

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AU - Nagarkatti, M.

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