Combinatorial Cytotoxic Effects of 2,3-Dichloro-5,8-dimethoxy-1,4-naphthoquinone and 4-hydroxytamoxifen in Triple-negative Breast Cancer Cell Lines.

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® 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.

• Authors: Anastasia G J Robinson, Yasmine M Kanaan, Robert L Copeland
• Journal: Anticancer research (Anticancer Res) Vol. 40 Issue 12 Pg. 6623-6635 (Dec 2020) ISSN: 1791-7530 [Electronic] Greece
• PMID: 33288557 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone
• Naphthoquinones
• Reactive Oxygen Species
• Tamoxifen
• afimoxifene

Topics

• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Synergism
• Female
• Humans
• Inhibitory Concentration 50
• Naphthoquinones (pharmacology)
• Reactive Oxygen Species (metabolism)
• Tamoxifen (analogs & derivatives, pharmacology)
• Triple Negative Breast Neoplasms (pathology)