Deciphering the effects of bixin on pulmonary alveolar adenocarcinoma migration and proliferation via targeting BAX/BCL-2 and Cyclin D1

There is a tremendous upsurge in lung cancer incidences due to changing lifestyles and other environmental risk factors. Unfortunately, the use of clinical therapeutics is causing serious side effects and drug-resistant tumors. Taking account of the severity of lung cancer malignancy and the pressing need for natural therapeutics, we investigated the anticancer potential of bixin in A549, pulmonary alveolar adenocarcinoma cell lines meticulously for the first time. Bixin is an apocarotenoid present in the seed arils of Bixa orellana known for its remarkable coloring utilities and high medicinal value. Here, we identified the cytotoxic and anti-migratory nature of bixin through MTT and scratch assay. Bixin also induced characteristic apoptotic morphological changes in cells which were distinguished through 4',6-diamidino-2-phenylindole (DAPI), and Acridine orange/Ethidium bromide (AO/EB) labeling. Bixin induced the mitochondrion-associated intrinsic apoptosis in A549 cells as evidenced in mitochondrial membrane potential assay, apoptosis assay, cell cycle analysis, and caspase assays. The relative gene expression studies proved that the bixin upregulated BAX, and downregulated BCL-2 and Cyclin D1. The in-silico analyses, molecular docking and molecular dynamics simulation underlined the interaction features of bixin and targeted proteins.