Background: Chinese herbal medicines have gained considerable interest from the cancer community as potential anti-tumor agents. Both clinical as well as pre-clinical studies have demonstrated that certain Chinese herbal medicines can improve survival, increase tumor response, improve quality of life, and reduce chemotherapy toxicity. The specific mechanisms by which these compounds mediate their effects remain largely unknown, inhibiting their development as clinical agents. One such compound is anethole. Anethole is an aromatic compound that occurs widely in nature as a component of anise, fennel anise myrtle, licorice, and star anise and is used in traditional Chinese medicine as an anti-inflammatory agent. Anethole has been identified as one of the potential phytochemicals with anti-cancer activities that could be developed into clinical treatments for breast cancers.Objective: In this current study, we evaluated the effect of anethole on physiological responses and specific survival pathways in human breast cancer MCF-7 cells.Results: Cell proliferation and cell survival were suppressed in a dose-dependent manner in response to anethole treatment, but these dosages had differential effect on specific pro-survival pathways. Anethole increased the cleavage of Poly (ADP-ribose) polymerase (PARP), suggesting an increase in apoptotic activity, but concurrently increased the expression of pro-survival proteins Bcl-2 and p21 while decreasing the expression of tumor suppressor protein p53. Phosphorylation of Akt kinase and S6 pro-survival proteins were modulated in an alternating pattern with increasing concentrations of anethole. Studies were also conducted to investigate the effect of anethole on the sensitivity of MCF-7 cells to tamoxifen treatments. The effect of tamoxifen on cell proliferation was not affected significantly by co-treatment with anethole but importantly the suppression of cell survival by tamoxifen was enhanced when anethole is present at a concentration of 10-5 M. Preliminary data suggest that one mechanism by which anethole is mediating some of its suppressive effects is through modulation of ER activity, as measured by luciferase assays. Studies are on-going to evaluate the relevance of this modulation to the inhibitory effects of anethole on the MCF-7 cells, as well as the modulation of the signal transduction pathways indicated on survival.Conclusion: These data suggest that the anethole is a potential anti-tumor agent, and that co-treatment of tamoxifen and anethole is a potential approach to sensitize human breast MCF-7 cells to tamoxifen treatments.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3100.