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EGCG, a major green tea catechin suppresses breast tumor angiogenesis and growth via inhibiting the activation of HIF-1α and NFκB, and VEGF expression.

Gu JW, Makey KL, Tucker KB, Chinchar E, Mao X, Pei I, Thomas EY, Miele L - (2013)

Bottom Line: EGCG treatment significantly reduced tumor weight over the control (0.37 ± 0.15 vs. 1.16 ± 0.30 g; P < 0.01), tumor CD (109 ± 20 vs. 156 ± 12 capillary #/mm^2; P < 0.01), tumor VEGF expression (45.72 ± 1.4 vs. 59.03 ± 3.8 pg/mg; P < 0.01), respectively.EGCG at 50 μg/ml significantly inhibited the activation of HIF-1α and NFκB as well as VEGF expression in cultured E0771 cells, compared to the control, respectively.These findings support the hypothesis that EGCG, a major green tea catechin, directly targets both tumor cells and tumor vasculature, thereby inhibiting tumor growth, proliferation, migration, and angiogenesis of breast cancer, which is mediated by the inhibition of HIF-1α and NFκB activation as well as VEGF expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. jgu@umc.edu.

ABSTRACT
The role of EGCG, a major green tea catechin in breast cancer therapy is poorly understood. The present study tests the hypothesis that EGCG can inhibit the activation of HIF-1α and NFκB, and VEGF expression, thereby suppressing tumor angiogenesis and breast cancer progression. Sixteen eight-wk-old female mice (C57BL/6 J) were inoculated with 10^6 E0771 (mouse breast cancer) cells in the left fourth mammary gland fat pad. Eight mice received EGCG at 50-100 mg/kg/d in drinking water for 4 weeks. 8 control mice received drinking water only. Tumor size was monitored using dial calipers. At the end of the experiment, blood samples, tumors, heart and limb muscles were collected for measuring VEGF expression using ELISA and capillary density (CD) using CD31 immunohistochemistry. EGCG treatment significantly reduced tumor weight over the control (0.37 ± 0.15 vs. 1.16 ± 0.30 g; P < 0.01), tumor CD (109 ± 20 vs. 156 ± 12 capillary #/mm^2; P < 0.01), tumor VEGF expression (45.72 ± 1.4 vs. 59.03 ± 3.8 pg/mg; P < 0.01), respectively. But, it has no effects on the body weight, heart weight, angiogenesis and VEGF expression in the heart and skeletal muscle of mice. EGCG at 50 μg/ml significantly inhibited the activation of HIF-1α and NFκB as well as VEGF expression in cultured E0771 cells, compared to the control, respectively. These findings support the hypothesis that EGCG, a major green tea catechin, directly targets both tumor cells and tumor vasculature, thereby inhibiting tumor growth, proliferation, migration, and angiogenesis of breast cancer, which is mediated by the inhibition of HIF-1α and NFκB activation as well as VEGF expression.

No MeSH data available.


Related in: MedlinePlus

The inhibition of the progression of breast cancer growth by oral EGCG in the immunocompetant female mice (C57BL/6) allografted with mouse breast cancer (E0771) cells. EGCG at 50 to 100 mg/kg/day in drinking water for four weeks significantly reduced a growth curve of breast cancer monitored by the tumor cross section area by 65% (Figure 1A, P < 0.01; n = 8) and tumor weight (Figure 1B, 0.37 ± 0.15 vs. 1.16 ± 0.30 g; P < 0.01; n = 8), compared to the control group.
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Figure 1: The inhibition of the progression of breast cancer growth by oral EGCG in the immunocompetant female mice (C57BL/6) allografted with mouse breast cancer (E0771) cells. EGCG at 50 to 100 mg/kg/day in drinking water for four weeks significantly reduced a growth curve of breast cancer monitored by the tumor cross section area by 65% (Figure 1A, P < 0.01; n = 8) and tumor weight (Figure 1B, 0.37 ± 0.15 vs. 1.16 ± 0.30 g; P < 0.01; n = 8), compared to the control group.

Mentions: We used a mouse breast cancer model that mimics the human disease, in which the mouse breast adenocinoma (E0771) cells were injected into the pad of the fourth mammary gland of female immunocompetent mice (C57BL/6). Immediately after the inoculation of E0771 cells, the eight week old female mice (n = 8) were given EGCG at 50 to 100 mg/kg/day in drinking water for four weeks and the control group (n = 8) was given regular drinking water only. Tumor size was then monitored every other day in two perpendicular dimensions parallel with the surface of the mice using dial calipers. As indicated in Figure 1A, the tumor cross section area was significantly reduced in the EGCG-treated group compared to the control group two weeks after the breast cancer inoculation. At the end of experiment, the tumor cross section area was reduced by 65% (P < 0.01) in EGCG-treated group compared to the control group (Figure 1A), which was consistent with the reduction in tumor weight (Figure 1B) in EGCG-treated group compared to the control group (0.37 ± 0.15 vs. 1.16 ± 0.30 g; P <0.01). Clearly, EGCG treatment at 50 to 100 mg/kg/d in drinking water significantly inhibited the progression of breast cancer growth in the female mice by decreasing the tumor size and reducing the growth curve of breast cancer. However, there was no significant difference in the body weight, heart weight, kidney weight, or urinary protein between the EGCG-treated mice and the control mice.


EGCG, a major green tea catechin suppresses breast tumor angiogenesis and growth via inhibiting the activation of HIF-1α and NFκB, and VEGF expression.

Gu JW, Makey KL, Tucker KB, Chinchar E, Mao X, Pei I, Thomas EY, Miele L - (2013)

The inhibition of the progression of breast cancer growth by oral EGCG in the immunocompetant female mice (C57BL/6) allografted with mouse breast cancer (E0771) cells. EGCG at 50 to 100 mg/kg/day in drinking water for four weeks significantly reduced a growth curve of breast cancer monitored by the tumor cross section area by 65% (Figure 1A, P < 0.01; n = 8) and tumor weight (Figure 1B, 0.37 ± 0.15 vs. 1.16 ± 0.30 g; P < 0.01; n = 8), compared to the control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3649947&req=5

Figure 1: The inhibition of the progression of breast cancer growth by oral EGCG in the immunocompetant female mice (C57BL/6) allografted with mouse breast cancer (E0771) cells. EGCG at 50 to 100 mg/kg/day in drinking water for four weeks significantly reduced a growth curve of breast cancer monitored by the tumor cross section area by 65% (Figure 1A, P < 0.01; n = 8) and tumor weight (Figure 1B, 0.37 ± 0.15 vs. 1.16 ± 0.30 g; P < 0.01; n = 8), compared to the control group.
Mentions: We used a mouse breast cancer model that mimics the human disease, in which the mouse breast adenocinoma (E0771) cells were injected into the pad of the fourth mammary gland of female immunocompetent mice (C57BL/6). Immediately after the inoculation of E0771 cells, the eight week old female mice (n = 8) were given EGCG at 50 to 100 mg/kg/day in drinking water for four weeks and the control group (n = 8) was given regular drinking water only. Tumor size was then monitored every other day in two perpendicular dimensions parallel with the surface of the mice using dial calipers. As indicated in Figure 1A, the tumor cross section area was significantly reduced in the EGCG-treated group compared to the control group two weeks after the breast cancer inoculation. At the end of experiment, the tumor cross section area was reduced by 65% (P < 0.01) in EGCG-treated group compared to the control group (Figure 1A), which was consistent with the reduction in tumor weight (Figure 1B) in EGCG-treated group compared to the control group (0.37 ± 0.15 vs. 1.16 ± 0.30 g; P <0.01). Clearly, EGCG treatment at 50 to 100 mg/kg/d in drinking water significantly inhibited the progression of breast cancer growth in the female mice by decreasing the tumor size and reducing the growth curve of breast cancer. However, there was no significant difference in the body weight, heart weight, kidney weight, or urinary protein between the EGCG-treated mice and the control mice.

Bottom Line: EGCG treatment significantly reduced tumor weight over the control (0.37 ± 0.15 vs. 1.16 ± 0.30 g; P < 0.01), tumor CD (109 ± 20 vs. 156 ± 12 capillary #/mm^2; P < 0.01), tumor VEGF expression (45.72 ± 1.4 vs. 59.03 ± 3.8 pg/mg; P < 0.01), respectively.EGCG at 50 μg/ml significantly inhibited the activation of HIF-1α and NFκB as well as VEGF expression in cultured E0771 cells, compared to the control, respectively.These findings support the hypothesis that EGCG, a major green tea catechin, directly targets both tumor cells and tumor vasculature, thereby inhibiting tumor growth, proliferation, migration, and angiogenesis of breast cancer, which is mediated by the inhibition of HIF-1α and NFκB activation as well as VEGF expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. jgu@umc.edu.

ABSTRACT
The role of EGCG, a major green tea catechin in breast cancer therapy is poorly understood. The present study tests the hypothesis that EGCG can inhibit the activation of HIF-1α and NFκB, and VEGF expression, thereby suppressing tumor angiogenesis and breast cancer progression. Sixteen eight-wk-old female mice (C57BL/6 J) were inoculated with 10^6 E0771 (mouse breast cancer) cells in the left fourth mammary gland fat pad. Eight mice received EGCG at 50-100 mg/kg/d in drinking water for 4 weeks. 8 control mice received drinking water only. Tumor size was monitored using dial calipers. At the end of the experiment, blood samples, tumors, heart and limb muscles were collected for measuring VEGF expression using ELISA and capillary density (CD) using CD31 immunohistochemistry. EGCG treatment significantly reduced tumor weight over the control (0.37 ± 0.15 vs. 1.16 ± 0.30 g; P < 0.01), tumor CD (109 ± 20 vs. 156 ± 12 capillary #/mm^2; P < 0.01), tumor VEGF expression (45.72 ± 1.4 vs. 59.03 ± 3.8 pg/mg; P < 0.01), respectively. But, it has no effects on the body weight, heart weight, angiogenesis and VEGF expression in the heart and skeletal muscle of mice. EGCG at 50 μg/ml significantly inhibited the activation of HIF-1α and NFκB as well as VEGF expression in cultured E0771 cells, compared to the control, respectively. These findings support the hypothesis that EGCG, a major green tea catechin, directly targets both tumor cells and tumor vasculature, thereby inhibiting tumor growth, proliferation, migration, and angiogenesis of breast cancer, which is mediated by the inhibition of HIF-1α and NFκB activation as well as VEGF expression.

No MeSH data available.


Related in: MedlinePlus