The Effects of Mibefradil in African American Triple Negative Breast Cancer Cells

Abstract ID 129904 Poster Board 058 More than one in ten women are affected globally by breast cancer (BC). Occurrence of BC differs among women of all ethnic groups and ages. The morbidity rate is the same in both European American (EA) and African American (AA) women however, in general the BC mortality rate is higher in AA women by 42%. Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. TNBC is a heterogeneous disease, and its tumors are characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Treatment options for this disease are limited and the five-year survival rate of TNBC is 6% lower in AA woman than other ethnicities. The store operated calcium entry (SOCE) mechanism has been implicated for TNBC progression, thus providing an innovative drug target for this disease. Gamma-butyrobetaine hydroxylase 1 (BBOX1) has been identified as an inositol 1, 4, 5-trisphosphate receptor type 3 (IP3R3) stabilizer in SOCE. We hypothesize that Mibefradil, a T- and L-type calcium channel blocker (CCB), causes apoptosis in the AA TNBC cell line HCC1806 via SOCE dysregulation. To determine this, cell proliferation assays, RT-PCR, and immunofluorescence were performed. Our results show a decrease in cell proliferation in HCC1806 cells with Mibefradil in a concentration- and time-dependent manner. Findings according to RT-PCR of gene expressions involved in calcium regulation suggest apoptosis in HCC1806 cells treated with Mibefradil. Results from immunofluorescence also depicted signs of apoptosis in HCC1806 cells treated with Mibefradil using the BBOX1 antibody. Taken together, these results suggest Mibefradil as a treatment option for TNBC. NIH/NCI; HU/Georgetown Collaborative Partnership in Cancer Research (5P20CA242611-0)