Molecular Investigation of the Antitumor Effects of Monoamine Oxidase Inhibitors in Breast Cancer Cells.

Abstract

The catalytic activity of monoamine oxidase A (MAO-A) has been linked to tumorigenesis due to the production of reactive oxygen species (ROS) and the resulting oxidative stress. MAO-A inhibition revealed a beneficial role in prostate and lung cancer treatment. This study is aimed at evaluating the effect of different monoamine oxidase A inhibitors (MAO-AIs) on the proliferation and progression of breast cancer cell lines. The cell viability assay was used to evaluate the antiproliferative and combined effects of MAO-AIs. Cell migration was evaluated using wound healing, invasion, and colony formation assays. The underlying mechanism of cell death was studied using flow cytometry. The real-time polymerase chain reaction was used to determine the relative gene expression. Finally, MAO-A activity in breast cancer cells was evaluated using an MAO-A activity assay. According to the results, the examined MAO-AIs significantly inhibited the proliferation of breast cancer cells in a dose-dependent manner. In breast cancer cells, the combination of anticancer drugs (doxorubicin or raloxifene) with MAO-AIs resulted in a synergistic effect. MAO-AIs significantly reduced wound closure and invasion ability in breast cancer cells. Also, MAO-AIs reduced the colony count and size of breast cancer cells. MAO-AIs resulted in significant proapoptotic activity in breast cancer cells. Finally, the MAO-AIs suppressed MAO-A, Bcl-2, and VEGF gene expressions in breast cancer cells relative to untreated cells. This study provides solid evidence supporting the anticancer effect of MAO-A inhibitors in breast cancer cells.