Enhanced susceptibility to apoptosis and growth arrest of human breast carcinoma cells treated with silica nanoparticles loaded with monohydroxy flavone compounds

Abstract

The treatment of drug-resistant cancer is a clinical challenge, hence screening for novel anticancer drugs is critically important. In this study, we investigated the anti-tumor potential of three plant-derived flavone compounds: 3-hydroxy flavone (3-HF), 6-hydroxy flavone (6-HF), and 7-hydroxy flavone (7-HF), either alone or combined with silica nanoparticles (3-HF + NP, 6-HF + NP, and 7-HF + NP), on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as on non-tumorigenic normal breast epithelial cells (MCF-10). The IC50values of these flavone compounds loaded with NP (flavones + NP) in these cell lines were determined to be 1.5 μg/mL without affecting the viability of normal MCF-10 cells. Additionally, using annexin V – propidium iodide double-staining followed by flow cytometry analysis, we found that the combination of flavones with NP significantly induced apoptosis in MCF-7 and MDA-MB-231 cancer cells. Furthermore, flavones + NP increased the expression of cytochrome c and caspase-9, mediating the growth arrest of these cancer cells. Most importantly, the combination of flavones with NP significantly abolished the expression of ATF-3, which is responsible for the proliferation and invasion of bone-metastatic breast cancer cells. Our data revealed the potential therapeutic effects of these flavones in fighting breast cancer cells, and provide the first insights concerning the underlying molecular mechanisms.