J Breast Cancer.  2009 Jun;12(2):85-91. 10.4048/jbc.2009.12.2.85.

Ellagic Acid Shows Different Anti-proliferative Effects Between the MDA-MB-231 and MCF-7 Human Breast Cancer Cell Lines

• Kim HA
• Lee RA
• Moon BI
• Choe KJ

• KMID: 2175202
• DOI: http://doi.org/10.4048/jbc.2009.12.2.85

Abstract

PURPOSE: It has been demonstrated ellagic acid can inhibit tumor growth. However, the mechanism that elicits the anti-proliferative effect of ellagic acid is poorly understood. Our objective in this study was to evaluate the biological activity of ellagic acid by comparing the anti-proliferative effect and the apoptotic pathway of ellagic acid between the 2 human breast cancer cell lines.
METHODS
The MCF-7 and MDA-MB-231 human breast cancer cell lines were used as cell models. The anti-proliferstive effect was evaluated by using a MTT assay. The cell cycle was analyzed by flow cytometry. Western blotting was performed to show the expressions of bcl-xL, cytochrome c, surviving, c-fos and pS2.
RESULTS
The ellagic acid in the MDA-MB-231 cells showed significant anti-proliferative effects with dose dependent pattern. The anti-proliferative effects in MCF-7 cells were observed in only at a high concentration. Ellagic acid had no effect on the cell cycle in both breast cancer cells. In MDA-MB-231, the expression of bcl-xL was decreased with the decreasing concentration of ellagic acid. The expression of cytochrome c in the cytosol was increased with the decreased expression of bcl-xL. Ellagic acid also decreased the expression of survivin. In the MCF-7 cells, the expressions of bcl-xL and cytochrome c showed no change after treatment with ellagic acid even at a high dose. Ellagic acid was able to induce an up-regulation of c-fos and pS2 protein in MCF-7.
CONCLUSION
Ellagic acid has an anti-proliferative effect in the MDA-MB-231 cells. This effect of ellagic acid is through the intrinsic pathway in MDA-MB-231 cells. However, the expression of bcl-xL showed no change in the MCF-7 cells. Ellagic acid has a different anti-proliferative effect between the two human breast cancer cell lines.

Keyword

Anti-proliferative effect; bcl-xL; Breast cancer; Ellagic acid; Survivin

MeSH Terms

Blotting, Western
Breast
Breast Neoplasms
Cell Cycle
Cell Line
Cytochromes c
Cytosol
Ellagic Acid
Flow Cytometry
Humans
MCF-7 Cells
Up-Regulation
Cytochromes c
Ellagic Acid

Figure

• 

  Figure 1 The concentration-dependent effects of ellagic acid on proliferation of human breast cancer cell lines. Cells were exposed to different concentrations of ellagic acid for 24 hr. Then, cell proliferation was evaluated by MTT assay. The tests were performed in more than three times and the error bars designate the SEM. The asterisk indicates significant difference (p<0.05) compared to control cells (0 µM) by the Tukey test.

• 

  Figure 2 The concentration-dependent effects of ellagic acid on proliferation of human breast cancer cell lines. Cells were exposed to different concentrations of ellagic acid for 24 hr. Then, cell proliferation was evaluated by MTT assay. The tests were performed in more than three times and the error bars designate the SEM. An asterisk indicates significant difference (p<0.05) compared to control cells (0 µM) by the Tukey test. (A) MDA-MB-231 cell line (B) MCF-7 cell line.

• 

  Figure 3 Effects of ellagic acid on cell cycle kinetics in human breast cancer cell lines. The tests were performed in more than three times and the error bars designate the SEM. (A) MDA-MB-231 cells, (B) MCF-7 cells.

• 

  Figure 4 Effects of ellagic acid on expression of bcl-xL, cytochrome c and survivin in human breast cancer cell lines. Cells were cultured and treated with each dose ellagic acid for 24 hr. The asterisk indicates statistical significance (p<0.05) from control cells (0 µM) after 24 hr after treatment by Mann Whitney test. (A) Western blot analysis of bcl-xL upon treatment with ellagic acid. (B) Western blot analysis of cytochrome c release from mitochondria into the cytosol in MDA-MB-231 cells upon treatment with ellagic acid. (C) Western blot analysis of survivin upon treatment with ellagic acid.

• 

  Figure 5 Effect of ellagic acid on expression of c-fos and pS2. Cells were stimulated for 48 hr with each dose of chemicals. Western blotting of pS2 and c-fos was done.

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