Abstract B030: Comparative analysis of cell viability of two triple-negative breast cancer cell lines using 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone and 4 hydroxy-tamoxifen

Abstract

Triple-negative breast cancer (TNBC) is classified as a form of breast cancer in which cells do not express estrogen receptor α (ERα), progesterone receptor, and human epidermal growth factor receptor 2 (HER2). This type of cancer affects African American women disproportionately to Caucasian women. The absence of these receptors make treatment of TNBC difficult because hormonal therapy, i.e., estrogen antagonist, progesterone antagonist and anti-HER2, is ineffective. TNBC frequently presents with elevated growth factor receptor expression and/or signaling with a resultant increase in mitogen activated kinase (MAPK) signaling, thus causing repression of ERα expression in a reversible manner. Based on these observations, the hypothesis is that the attenuation of the MAPK pathway by direct inhibition of hyperactivated MAPK will result in re-expression and functionality of ERα using 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone (Z285), making cells susceptible to conventional antiestrogen therapy. Experiments were performed using TNBC cell lines (MDA MB 231 and HCC1806) derived from Caucasian and African American women, respectively, in concentration- and time-dependent assays. Cells were treated with Z285 alone and in combination with 4 hydroxy tamoxifen (4OH-Tam) and showed an increase in cell death using cell viability assay. Results show a stark difference in the effect of the two drugs on the two cell lines when given alone. From 24-120 hours the Z285 had minimal effect on both MDA-MB 231 and HCC 1806 cell lines with IC-50 above the highest concentrations given; however, the 4-OH Tam caused significant cell death, particularly at 72 to 120 hours with IC50 values of 6 μM. The combination study of pretreating the cells of 2 μM and 5 μM Z285 followed by 4 OH-Tam showed a significant decrease in the cell viability in the HCC 1806 cells with IC50s of 7 μM at 24 hours where the MDA-MB 231 cells were more resistant at 24 hours. The 72-120 hours showed significant concentration- and time-dependent decreases in cell viability for both cell types. Particularly, the HCC 1806 were more sensitive to the effects of 4-OH Tam with IC50 at 1 μM compared to MDA-MB 231 IC50 of 5 μM at 120 hours at both 2 μM and 5 μM pretreatment. Taken together, these drugs may work synergistically to promote cell death, thus providing a new potential avenue for therapy. Therefore, patients suffering from TNBC could benefit from combinational treatment with Z285 or its analogs and conventional chemo/hormonal therapy. Citation Format: Anastasia G.J. Robinson, Ridge Wells, Samantha J. Wilkinson, Robert L. Copeland. Comparative analysis of cell viability of two triple-negative breast cancer cell lines using 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone and 4 hydroxy-tamoxifen [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B030.