Abstract
Breast cancer is the leading cause of cancer related death in women. Quercetin is a flavonol shown to have anti-carcinogenic 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 efficacious 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.
Keywords:
BW, body weight; DCIS, ductal carcinoma in situ; DEPTOR, DEP domain containing mTOR-interacting protein; DEXA, dual-energy X-ray absorptiometry; ERα, estrogen receptor alpha; FABP7, fatty acid binding protein-7; GREB1, growth regulation by estrogen in breast cancer; MIN, mammary intraepithelial neoplasia; Muc13, Mucin 13; NGFR, nerve growth factor receptor; TIMP4, tissue inhibitor of metalloproteinases-4; TMPRSS4, transmembrane protease serine 4; dose-response; flavonoid; gene expression microarray; krt6a/b, keratin 6A/B; mammary tumorigenesis.