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Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo.

Tran PL, Kim SA, Choi HS, Yoon JH, Ahn SG - BMC Cancer (2010)

Bottom Line: The aim of this study was to examine the effect of EGCG on the expression of heat shock proteins (HSPs) and tumor suppression.Treatment with EGCG decreased cell proliferation and colony formation of MCF-7 human breast cancer cells.Moreover, treatment with EGCG (10 mg/kg) in a xenograft model resulted in delayed tumor incidence and reduced tumor size, as well as the inhibition of HSP70 and HSP90 expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Chosun University, College of Dentistry, Gwangju 501-759, Republic of Korea.

ABSTRACT

Background: Epigallocatechin-3-gallate (EGCG), one of the major catechins in green tea, is a potential chemopreventive agent for various cancers. The aim of this study was to examine the effect of EGCG on the expression of heat shock proteins (HSPs) and tumor suppression.

Methods: Cell colony formation was evaluated by a soft agar assay. Transcriptional activity of HSP70 and HSP90 was determined by luciferase reporter assay. An EGCG-HSPs complex was prepared using EGCG attached to the cyanogen bromide (CNBr)-activated Sepharose 4B. In vivo effect of EGCG on tumor growth was examined in a xenograft model.

Results: Treatment with EGCG decreased cell proliferation and colony formation of MCF-7 human breast cancer cells. EGCG specifically inhibited the expression of HSP70 and HSP90 by inhibiting the promoter activity of HSP70 and HSP90. Pretreatment with EGCG increased the stress sensitivity of MCF-7 cells upon heat shock (44 degrees C for 1 h) or oxidative stress (H2O2, 500 microM for 24 h). Moreover, treatment with EGCG (10 mg/kg) in a xenograft model resulted in delayed tumor incidence and reduced tumor size, as well as the inhibition of HSP70 and HSP90 expression.

Conclusions: Overall, these findings demonstrate that HSP70 and HSP90 are potent molecular targets of EGCG and suggest EGCG as a drug candidate for the treatment of human cancer.

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Related in: MedlinePlus

EGCG represses the growth of tumor in mice. BALB/c mice were subcutaneously injected with 5 × 106 colon carcinoma CT26 cells into the right flank. After 4 days, the mice were given daily dose of PBS or EGCG (10 mg/kg) through intraperitoneal injection for 7 days as described in "Methods" section. (A), (B) Serial tumor volumes and body weights were measured everyday. Values represent mean ± SD. (C) Representative images of xenograft tumors.
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Figure 6: EGCG represses the growth of tumor in mice. BALB/c mice were subcutaneously injected with 5 × 106 colon carcinoma CT26 cells into the right flank. After 4 days, the mice were given daily dose of PBS or EGCG (10 mg/kg) through intraperitoneal injection for 7 days as described in "Methods" section. (A), (B) Serial tumor volumes and body weights were measured everyday. Values represent mean ± SD. (C) Representative images of xenograft tumors.

Mentions: The anti-tumor efficacy of EGCG was examined on a mouse xenograft model using CT26 colon cancer cells. CT26 cells were injected subcutaneously in BALB/c mice. After the palpable tumors were appeared (4 days after injection), EGCG (10 mg/kg) was injected intraperitoneally every day for 7 days. As shown in Figure 6A, the administration of EGCG caused a 70% decrease in tumor volume compared with PBS-treated control mice. The toxicity of EGCG was assessed by mouse survival and careful monitoring of body weight. The EGCG treatment did not alter body weight compared with PBS-treated control mice (Figure 6B).


Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo.

Tran PL, Kim SA, Choi HS, Yoon JH, Ahn SG - BMC Cancer (2010)

EGCG represses the growth of tumor in mice. BALB/c mice were subcutaneously injected with 5 × 106 colon carcinoma CT26 cells into the right flank. After 4 days, the mice were given daily dose of PBS or EGCG (10 mg/kg) through intraperitoneal injection for 7 days as described in "Methods" section. (A), (B) Serial tumor volumes and body weights were measured everyday. Values represent mean ± SD. (C) Representative images of xenograft tumors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927993&req=5

Figure 6: EGCG represses the growth of tumor in mice. BALB/c mice were subcutaneously injected with 5 × 106 colon carcinoma CT26 cells into the right flank. After 4 days, the mice were given daily dose of PBS or EGCG (10 mg/kg) through intraperitoneal injection for 7 days as described in "Methods" section. (A), (B) Serial tumor volumes and body weights were measured everyday. Values represent mean ± SD. (C) Representative images of xenograft tumors.
Mentions: The anti-tumor efficacy of EGCG was examined on a mouse xenograft model using CT26 colon cancer cells. CT26 cells were injected subcutaneously in BALB/c mice. After the palpable tumors were appeared (4 days after injection), EGCG (10 mg/kg) was injected intraperitoneally every day for 7 days. As shown in Figure 6A, the administration of EGCG caused a 70% decrease in tumor volume compared with PBS-treated control mice. The toxicity of EGCG was assessed by mouse survival and careful monitoring of body weight. The EGCG treatment did not alter body weight compared with PBS-treated control mice (Figure 6B).

Bottom Line: The aim of this study was to examine the effect of EGCG on the expression of heat shock proteins (HSPs) and tumor suppression.Treatment with EGCG decreased cell proliferation and colony formation of MCF-7 human breast cancer cells.Moreover, treatment with EGCG (10 mg/kg) in a xenograft model resulted in delayed tumor incidence and reduced tumor size, as well as the inhibition of HSP70 and HSP90 expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Chosun University, College of Dentistry, Gwangju 501-759, Republic of Korea.

ABSTRACT

Background: Epigallocatechin-3-gallate (EGCG), one of the major catechins in green tea, is a potential chemopreventive agent for various cancers. The aim of this study was to examine the effect of EGCG on the expression of heat shock proteins (HSPs) and tumor suppression.

Methods: Cell colony formation was evaluated by a soft agar assay. Transcriptional activity of HSP70 and HSP90 was determined by luciferase reporter assay. An EGCG-HSPs complex was prepared using EGCG attached to the cyanogen bromide (CNBr)-activated Sepharose 4B. In vivo effect of EGCG on tumor growth was examined in a xenograft model.

Results: Treatment with EGCG decreased cell proliferation and colony formation of MCF-7 human breast cancer cells. EGCG specifically inhibited the expression of HSP70 and HSP90 by inhibiting the promoter activity of HSP70 and HSP90. Pretreatment with EGCG increased the stress sensitivity of MCF-7 cells upon heat shock (44 degrees C for 1 h) or oxidative stress (H2O2, 500 microM for 24 h). Moreover, treatment with EGCG (10 mg/kg) in a xenograft model resulted in delayed tumor incidence and reduced tumor size, as well as the inhibition of HSP70 and HSP90 expression.

Conclusions: Overall, these findings demonstrate that HSP70 and HSP90 are potent molecular targets of EGCG and suggest EGCG as a drug candidate for the treatment of human cancer.

Show MeSH
Related in: MedlinePlus