Roots of Daphne gnidium L. inhibit cell proliferation and induce apoptosis in the human breast cancer cell line MCF-7

Daphne gnidium L. is a well-known Moroccan plant with cancer-related ethnobotanical use. In order to systematically evaluate its potential activity in breast cancer, four extracts from this plant of different polarity were tested for their antiproliferative effects on MCF-7 cells. The second aspect of this study related to understanding the nature and mechanism of the antiproliferative effect. Results from a viability assay showed the potent antiproliferative capacity of the hexane (IC(50)-48 h: 630 +/- 16 microg/ml), dichloromethane (IC(50)-48 h: 112 +/- 7 microg/ml) and ethyl acetate extracts (IC(50)-48 h: 263 +/- 9 microg/ml). On the other hand the methanol extract was inactive. LDH test revealed the cytotoxicity of the hexane extract as opposed to two others. The characterization of the ethyl acetate extract showed its dose-dependent pro-apoptotic effect. Surprisingly, we observed that activation of the inducible cyclooxygenase-2 followed the kinetics of apoptosis development. On the other hand, the dichloromethane extract showed a distinct effect on COX-2 activity as a function of the used dose. A low dose seemed to inhibit COX-2 activity whereas a high dose seemed to increase it. These findings suggest that Daphne gnidium L. might be of potential chemopreventive interest. Other studies are in hand to isolate the active agents responsible for the antiproliferative effect.