@article {ROBINSON6623, author = {ANASTASIA G.J. ROBINSON and YASMINE M. KANAAN and ROBERT L. COPELAND}, title = {Combinatorial Cytotoxic Effects of 2,3-Dichloro-5,8-dimethoxy-1,4-naphthoquinone and 4-hydroxytamoxifen in Triple-negative Breast Cancer Cell Lines}, volume = {40}, number = {12}, pages = {6623--6635}, year = {2020}, doi = {10.21873/anticanres.14687}, publisher = {International Institute of Anticancer Research}, abstract = {Background/Aim: 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. Materials and Methods: 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. Results: 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{\textregistered} showed additive effects in MCF7, HCC1806 and Hs578T and an antagonistic response in MDA-MB-231. Z285 caused a significant increase in ROS production in three cell lines after 8 h, but HCC1806 showed no change in effect. Conclusion: 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.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/40/12/6623}, eprint = {https://ar.iiarjournals.org/content/40/12/6623.full.pdf}, journal = {Anticancer Research} }