Inhibition of malate dehydrogenase via nanoselenium coupling with nanocellulose composite in MCF-7 breast carcinoma cells

Abstract

Background Cancer, a leading cause of mortality worldwide, continues to pose significant challenges in treatment and management. Conventional therapies often face limitations, including lack of selectivity, adverse effects, and the development of resistance mechanisms. Methods Therefore, this study aims to investigate nanocellulose, nanoselenium, and their nanocomposite which are previously synthesized and characterized. Molecular docking simulations were performed to assess binding affinity to malate dehydrogenase-1 (MDH-1), a key metabolic enzyme in cancer cells. Cytotoxicity was evaluated in A549 lung cancer cell line, the MCF-7 breast cancer cell line, and the WI-38 normal cell line. Mechanistic studies included assessment of MDH-1 activity and expression, intracellular reactive oxygen species (ROS) levels, and cell cycle analysis. Results Molecular docking simulations demonstrated a favorable binding affinity (136.98 kcal/mol) of cellulose and selenium as cofactor to the nicotinamide adenine dinucleotide (NAD) + hydrogen (H) (NADH) binding domain of human MDH-1. The nanocomposite exhibited a synergistic impact against cancer, causing a considerable decrease in the viability of MCF-7 cells compared to separate treatments with nanocellulose and nanoselenium. Moreover, it showed negligible toxicity towards normal cells. Biochemical studies demonstrated that nanocellulose, nanoselenium and the nanocomposite substantially reduced MDH-1 activity and messenger ribonucleic acid (mRNA) expression in MCF-7 cells. This was confirmed by flow cytometric analysis, which revealed that the nanocomposite could effectively reduce the intracellular ROS levels and induce potent cell cycle arrest in the G0/G1 phase, that inhibit MCF-7 cell proliferation. Conclusions In conclusion, our finding elucidated the promising therapeutic potential of nanocellulose, nanoselenium, and their nanocomposite as effective anticancer agents in breast cancer treatment, demanding further preclinical and clinical investigations to explain their mechanisms of action.