Oleuropein's anti-cancer effect on MDA-MB-231 breast cancer cells is mediated through DNA damage and is independent of Estrogen Receptors alpha and beta

Oleuropein the main polyphenol of olive leaf and oil has been shown recently to possess anti-cancer properties [1]. The objective of the present study was to evaluate the anticancer effect of oleuropein in breast cancer and determine the mechanism of its action. Two breast cancer cell lines were used, the Estrogen Receptor negative MDA-MB-231 and the Estrogen Receptor positive MCF-7. We have also examined the normal but immortalized breast cell line MCF-10A. Twenty-four hours after oleuropein addition (at concentrations 10–100µg/ml) there was a concentration dependent decrease in the survival of the cells. Interestingly, the growth of MCF-7 or normal MCF-10A cells was not affected by the same concentrations of oleuropein even after 72h of treatment. The selective killing of MDA-MB-231 cells by oleuropein apparently is due to DNA breakage which became evident within 2h of treatment. Predictably, DNA damage was not evident in MCF-10A cells after 24h of incubation. To determine if the estrogen receptors protected cells from DNA damage, we evaluated the response of the ER alpha (S30), and ER beta (ERβ41) transfectants (from MDA-MB-231 parental cells) to oleuropein. These transfectants were as susceptible to cell death as their parental cells, suggesting that the estrogen receptors alpha and beta do not provide protection against oleuropein-induced cell death. The selective DNA damaging and anti-proliferative effect of oleuropein on ER negative MDA-MB-231 cells is intriguing and the elucidation of its exact mechanism of cell killing might provide important clues to the anticancer properties of this polyphenol. These data suggest that the olive mill waste containing oleuropein may be a source of important and selective anticancer agents.

Acknowledgements: This research was partially funded by the Cyprus Research Promotion Foundation.

References: 1. Hamdi, HK., Castellon, R. (2005) Biochem. Biophys. Res. Commun. 334:769–78.