Effects of zinc oxide nanoparticles on pyruvate dehydrogenase and lactate dehydrogenase expressions and apoptotic index in breast cancer cells

Abstract

Zinc oxide nanoparticles (ZnO-NPs) are metal oxide NPs that have high cytotoxicity on cancer cells and low cytotoxicity on healthy cells. Breast cancer is the most frequent type of cancer-causing death among women worldwide. In this study, anti-cancer effects of ZnO-NPs were investigated. For this purpose, we treated the MCF7 and MDA-MB-231 breast cancer cell lines and human umbilical vein endothelial cells HUVEC cell line with 10 μg/mL and 20 μg/mL ZnO-NP. Anti-cancer effects of ZnO-NPs were evaluated with cell viability, apoptotic index and colony formation assays, and anti-Warburg effect were investigated by evaluating of pyruvate dehydrogenase (PDH) and Lactate Dehydrogenase A (LDHA) protein expressions. Results indicated that, ZnO-NP application did not have a cytotoxic effect on HUVEC cells, it had cytotoxicity on both breast cancer cell lines. However, MCF7 cells were more sensitive to ZnO-NP treatment. Administration of 20 μg/mL ZnO-NP reduced the survival of MCF7 cells by 62% and increased the apoptotic index by approximately 6 times. Additionally, ZnO-NP treatment inhibited the doubling times of cells and suppressed the colony-forming abilities of both breast cancer cell lines. Also, it was seen that ZnO-NP treatment increased PDH expression in MCF7 cells, where the apoptotic index was more induced. As a result, we have shown for the first time that ZnO-NPs affect the energy metabolism of cells by increasing PDH expression in MCF7 cells, thus increasing the apoptotic index. Our study, which observed the anticancer effects of ZnO-NPs on breast cancer cells, will also shed light on future experimental studies.

Keywords

• breast cancer
• lactate dehydrogenase a
• mda-mb-231
• mcf7
• pyruvate dehydrogenase
• zinc oxide nanoparticles