Effect of Ursolic Acid, Selenium Nanoparticles, and Their Combination on the Metastasis-Associated Gene Expression in MDA-MB-231 Breast Cancer Cells: In-vitro Study

Abstract

Abstract Metastasis is a leading cause of cancer-related mortality. Triple-negative human breast carcinoma (TNBC) exhibits increased invasion and metastatic activity compared to other types of breast cancer, often resulting in a poor prognosis. The aim of this study was to examine the impact of selenium nanoparticles (SeNPs), ursolic acid, and their combination on the MDA-MB-231 TNBC cell line in terms of their potential antiproliferative and antimetastatic effects. The cytotoxic effect of the aforementioned substances was evaluated using an MTT assay. Additionally, their impact on the expression levels of ICAM-1, a transmembrane glycoprotein that promotes metastasis, and two matrix metalloproteinases (MMP-2 and MMP-9) that are essential for tumor invasion and migration, was investigated by using real-time PCR. Moreover, the scratch assay was used to observe cell migration after SeNPs and ursolic acid treatment. The findings suggest that although applying 150 µg/mL SeNPs and 20 µg/mL UA separately revealed more cell inhibition rate, a combination group of SeNPs and ursolic acid not only decreases the viability of cancer cells in comparison to the control group, but also harbors synergistic actions in reducing the migration and metastasis of MDA-MB-231 cells by their most effective downregulation of MMP-9, MMP-2, and ICAM-1 expression. It can be considered a novel potential treatment for triple-negative metastatic breast cancer (TNBC). However for better justification of this mechanism, more detailed studies on animal models should be performed.