Introduction: Triple negative breast cancer (TNBC) is a subtype of breast cancer that lacks the three receptors that current therapy targets (estrogen (ER), progesterone, HER2). Because of this, it is a very aggressive type of breast cancer with a high mortality rate. In a previous study, we discovered the drug, riluzole, to be an mGluR1 inhibitor and to reduce cell proliferation and tumor growth in triple negative breast cancer (TNBC), resulting in apoptosis. This was a significant finding because there are currently no major therapies available to successfully treat TNBC. It is now being thought that riluzole also has properties that may allow it to act as a therapy against ER-positive breast cancer (ER+).
Methods: The goal of this study was to learn more about how riluzole functions by analyzing the anti-oncogenic properties of riluzole. To do this, we conducted a series of transformation assays including cell proliferation (MTT), invasion, soft agar, adhesion, and in vivo metastasis using 4T1-12B cells (a luciferase-expressing clone of the 4T1 mouse mammary tumor cell line).
Results: The results of the assays completed thus far indicate that both TNBC and ER+ cells are sensitive to riluzole, with TNBC being more sensitive. Riluzole significantly inhibits invasion of TNBC cells but not ER+ cells. These findings are consistent with the previous study's results showing that riluzole targets mGluR1 pathways, since ER+ cells contain significantly smaller amounts of mGluR1 compared to TNBC cells. Additionally, riluzole inhibits both cell proliferation and anchorage independent growth of both cell types, suggesting both mGluR1 dependent and independent pathways are involved.
Conclusion: The results of this study suggest that riluzole can be developed as an anti-breast cancer therapy for both triple negative and ER-positive breast cancer patients. Further studies silencing mGluR1 in TNBC and overexpressing mGluR1 in ER+ cell lines will help to determine any significance of mGluR1 in mediating riluzole's mechanism of action.
Citation Format: Miriam A. Bukhsh, Cecilia L. Speyer, Ali A. Hachem, Mahdy Nassar, Ali A. Assi, David H. Gorski. Exploring anti-oncogenic properties of riluzole in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4608. doi:10.1158/1538-7445.AM2014-4608