Linarin inhibits survival and metastasis in triple-negative breast cancer cell line MDA-MB-231 by downregulating NF-κB p-p65/MMP-9, upregulating Bax, and enhancing Caspase 3/7 expression

Triple Negative Breast Cancer (TNBC) is an aggressive type of breast cancer that is responsible for most of the cancer related deaths in women. Traditional two-dimensional (2D) cell cultures are insufficient to mimic the complex tumour environment, so three-dimensional (3D) spheroid cultures are used to provide a more accurate model. Our study explores the anticancer and antimetastatic effects of linarin on TNBC cell line MDA-MB-231 cells. We conducted experiments using both 2D and 3D cultured cells. Linarin treatment reduced cell viability (2D IC₅₀:120.8 µM ***<i>p</i> &lt; 0.001, 3D IC₅₀: 1949 µM ****<i>p</i> &lt; 0.0001 respectively) and migration (***<i>p</i> &lt; 0.001, ****<i>p</i> &lt; 0.0001), increased apoptosis, and upregulated Bax and Caspase3/7 protein levels (****<i>p</i> &lt; 0.0001). It also reduced p-p65 and MMP-9 protein expression levels (****<i>p</i> &lt; 0.0001), suggesting possible suppression of survival and metastatic pathways. Linarin also led to a loss of spheroid compactness suggesting interference with its cancer-promoting activities. These findings suggest that linarin could be a promising therapeutic option for TNBC.