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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

Histological and immunohistochemical appearance of tumors from CT26 cell-injected mice. Mice were subcutaneously injected with CT26 cells into the right flank. Four days later, mice were treated with either PBS (control) or EGCG for 7 days. (A) H & E staining and immunohistochemical staining of PCNA, HSP70, and HSP90 for tumor sections. (B) The levels of HSP70 and HSP90 in the lysates of tumor tissues were analyzed by Western blot analysis. Western blot data were quantified by densitometry. The data were expressed as the mean ± SD of three individual experiments.
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Figure 7: Histological and immunohistochemical appearance of tumors from CT26 cell-injected mice. Mice were subcutaneously injected with CT26 cells into the right flank. Four days later, mice were treated with either PBS (control) or EGCG for 7 days. (A) H & E staining and immunohistochemical staining of PCNA, HSP70, and HSP90 for tumor sections. (B) The levels of HSP70 and HSP90 in the lysates of tumor tissues were analyzed by Western blot analysis. Western blot data were quantified by densitometry. The data were expressed as the mean ± SD of three individual experiments.

Mentions: To examine whether EGCG is able to inhibit the expression of HSP70 and HSP90 in vivo, the tumor tissues were excised. Immunohistochemistry assay showed that the levels of HSP70 and HSP90 were decreased in EGCG-treated mice compared with control (Figure 7A). The expression of PCNA, a proliferation biomarker, also significantly decreased (approximately 50%). Western blot analysis showed that the expression levels of HSP70 and HSP90 were decreased in EGCG-treated mice compared with control (Figure 7B).


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)

Histological and immunohistochemical appearance of tumors from CT26 cell-injected mice. Mice were subcutaneously injected with CT26 cells into the right flank. Four days later, mice were treated with either PBS (control) or EGCG for 7 days. (A) H & E staining and immunohistochemical staining of PCNA, HSP70, and HSP90 for tumor sections. (B) The levels of HSP70 and HSP90 in the lysates of tumor tissues were analyzed by Western blot analysis. Western blot data were quantified by densitometry. The data were expressed as the mean ± SD of three individual experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Histological and immunohistochemical appearance of tumors from CT26 cell-injected mice. Mice were subcutaneously injected with CT26 cells into the right flank. Four days later, mice were treated with either PBS (control) or EGCG for 7 days. (A) H & E staining and immunohistochemical staining of PCNA, HSP70, and HSP90 for tumor sections. (B) The levels of HSP70 and HSP90 in the lysates of tumor tissues were analyzed by Western blot analysis. Western blot data were quantified by densitometry. The data were expressed as the mean ± SD of three individual experiments.
Mentions: To examine whether EGCG is able to inhibit the expression of HSP70 and HSP90 in vivo, the tumor tissues were excised. Immunohistochemistry assay showed that the levels of HSP70 and HSP90 were decreased in EGCG-treated mice compared with control (Figure 7A). The expression of PCNA, a proliferation biomarker, also significantly decreased (approximately 50%). Western blot analysis showed that the expression levels of HSP70 and HSP90 were decreased in EGCG-treated mice compared with control (Figure 7B).

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