naphthoquinones and afimoxifene

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer (BC) and lacks targeted therapy and alternate therapeutic combinations. There is a necessity to increase disease-free survival in patients particularly within the first 5 years of diagnosis. 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone (Z285), a novel 1,4 naphthoquinone analog, has been shown to have cytotoxic activity in BC cell lines and in combination with 4-hydroxytamoxifen (4-OHT). A known metabolite of tamoxifen, was postulated to decrease cell proliferation. Thus, this study investigates the use of Z285 and 4-OHT alone or in combination as a novel therapeutic alternative for TNBC.. Cell proliferation assays were performed on MDA-MB-231, Hs578T, MCF7 and HCC1806 cell lines at varying time points with Z285 and 4-OHT alone and in combination. Furthermore, ROS activity was measured to determine the changes in oxidative stress caused by both drugs.. The results showed dose- and time-dependent decreases in proliferation for all cell lines when treated with Z285, 4-OHT and their combination. Combinatorial analysis performed at 72 h using Synergyfinder. These promising results suggest the independent ability of each compound as a stand-alone chemotherapeutic agent, or in combinatorial therapy for the treatment of TNBC.

Topics: Apoptosis; Cell Line, Tumor; Cell Survival; Drug Synergism; Female; Humans; Inhibitory Concentration 50; Naphthoquinones; Reactive Oxygen Species; Tamoxifen; Triple Negative Breast Neoplasms