Inhibition of breast cancer cell development using Citrus maxima extract through increasing levels of Reactive Oxygen Species (ROS)

Abstract

Excessive Reactive oxygen species (ROS) level can lead to the activation of apoptosis and inhibit metastasis through the NF-κB pathway. Therapeutic approaches by increasing ROS level may be effective strategic in cancer treatment. Citrus maxima (CM) is one of a natural medicinal plant that exhibits cytotoxic effect on several cancer cells. However, the CM extract effect to regulate ROS level remains unclear. Therefore, in this study aims to evaluated the cytotoxic effects of CM extract on metastasis breast cancer MDA-MD-231 cells. Cytotoxic activity of CM extract was evaluated using MTT assay, ROS levels was calculated under flowcytometry. Furthermore, the binding interaction between phytoconstituents and protein that responsible on the ROS metabolic pathway was analyzed under in silico molecular docking. The presence of CM extract increased cells death with IC50 value of 338 μg/mL for 24 h through induction of ROS levels. Molecular docking studies revealed that the hesperidin displayed the best binding energies at -21.4766 (NF-κB) kcal/mol. The binding interaction of hesperidin with the active site of NF-κB protein suggested that amino acid residues (His537, Asp519, Gly407, Gln479, Arg416) might play a role in ROS metabolism. These findings have shown that CM extract inhibited cancer proliferation by increasing ROS levels.