Anti-metastasis activity of 5,4’-dihydroxy 6,8-dimethoxy 7-O-rhamnosyl flavone from Indigofera aspalathoides Vahl on breast cancer cells

Abstract

Abstract Breast cancer presents a significant challenge due to its high rates of illness and mortality, necessitating more effective treatment approaches. While traditional treatments offer some benefits, they often lack precision in targeting cancer cells and can inadvertently harm healthy tissues. This study aims to investigate the cytotoxic effects and molecular mechanism of 5,4’-dihydroxy-6,8-dimethoxy-7-O-rhamnosyl flavone (DDR), extracted from Indigofera aspalathoides Vahl, on breast cancer cells (MDA-MB-231). Through various in vitro assays including wound healing, invasion, Western blotting, and immunofluorescence, the impact of DDR on epithelial-mesenchymal transition (EMT) and metastasis was evaluated. Treatment of MDA-MB-231 cells with different DDR concentrations (0–10 µg/mL) resulted in a significant decrease in invasion and migration, accompanied by the downregulation of metastasis-related proteins including VEGF, uPAR, uPA, and MMP-9. DDR treatment also hindered EMT by upregulating E-cadherin and downregulating N-cadherin, Slug, Twist, and Vimentin. Additionally, inhibition of the PI3K/AKT signaling pathway and downregulation of the NF-кB pathway were observed. These findings highlight the potential of DDR as a valuable source of natural compounds with promising anticancer properties, offering opportunities for the development of novel cancer therapies.

Keywords

• 5,4’-Dihydroxy-6,8-dimethoxy-7-O-rhamnosyl
• Indigofera aspalathoides
• Breast cancer
• Wnt/β-catenin
• PI3K/AKT