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

Abstract 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 th...

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Main Authors: Ressin Varghese, Siva Ramamoorthy
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-96788-9
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author Ressin Varghese
Siva Ramamoorthy
author_facet Ressin Varghese
Siva Ramamoorthy
author_sort Ressin Varghese
collection DOAJ
description Abstract 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 4ʹ,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.
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spelling doaj-art-8d81c520f467440e9f360aa42cfb3df72025-08-20T01:47:29ZengNature PortfolioScientific Reports2045-23222025-04-0115111610.1038/s41598-025-96788-9Deciphering the effects of bixin on pulmonary alveolar adenocarcinoma migration and proliferation via targeting BAX/BCL-2 and Cyclin D1Ressin Varghese0Siva Ramamoorthy1School of Bio Sciences and Technology, Vellore Institute of TechnologySchool of Bio Sciences and Technology, Vellore Institute of TechnologyAbstract 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 4ʹ,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.https://doi.org/10.1038/s41598-025-96788-9Lung cancerA549BixinApoptosisCyclin D1BAX
spellingShingle Ressin Varghese
Siva Ramamoorthy
Deciphering the effects of bixin on pulmonary alveolar adenocarcinoma migration and proliferation via targeting BAX/BCL-2 and Cyclin D1
Scientific Reports
Lung cancer
A549
Bixin
Apoptosis
Cyclin D1
BAX
title Deciphering the effects of bixin on pulmonary alveolar adenocarcinoma migration and proliferation via targeting BAX/BCL-2 and Cyclin D1
title_full Deciphering the effects of bixin on pulmonary alveolar adenocarcinoma migration and proliferation via targeting BAX/BCL-2 and Cyclin D1
title_fullStr Deciphering the effects of bixin on pulmonary alveolar adenocarcinoma migration and proliferation via targeting BAX/BCL-2 and Cyclin D1
title_full_unstemmed Deciphering the effects of bixin on pulmonary alveolar adenocarcinoma migration and proliferation via targeting BAX/BCL-2 and Cyclin D1
title_short Deciphering the effects of bixin on pulmonary alveolar adenocarcinoma migration and proliferation via targeting BAX/BCL-2 and Cyclin D1
title_sort deciphering the effects of bixin on pulmonary alveolar adenocarcinoma migration and proliferation via targeting bax bcl 2 and cyclin d1
topic Lung cancer
A549
Bixin
Apoptosis
Cyclin D1
BAX
url https://doi.org/10.1038/s41598-025-96788-9
work_keys_str_mv AT ressinvarghese decipheringtheeffectsofbixinonpulmonaryalveolaradenocarcinomamigrationandproliferationviatargetingbaxbcl2andcyclind1
AT sivaramamoorthy decipheringtheeffectsofbixinonpulmonaryalveolaradenocarcinomamigrationandproliferationviatargetingbaxbcl2andcyclind1