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.