Berberine nanostructures attenuate ß-catenin, a key component of epithelial mesenchymal transition in lung adenocarcinoma

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2023-12, Vol.396 (12), p.3595-3603
• Main Authors: Malyla, Vamshikrishna, De Rubis, Gabriele, Paudel, Keshav Raj, Chellappan, Dinesh Kumar, Hansbro, Nicole G., Hansbro, Philip M., Dua, Kamal
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma of Lung - drug therapy; Anti-inflammatory agents; Berberine; Berberine - pharmacology; Berberine - therapeutic use; beta Catenin - metabolism; Bioavailability; Biomedical and Life Sciences; Biomedicine; Catenins - metabolism; Cell fate; Cell growth; Cell Line, Tumor; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Homeostasis; Humans; Inflammation; Lung cancer; Lung Neoplasms - drug therapy; Metastases; Metastasis; Molecular modelling; Nanoparticles; Nanostructures; Neurosciences; Pharmacology/Toxicology; Proteins; Wnt Signaling Pathway; β-Catenin
• ISSN: 0028-1298; 1432-1912; 1432-1912
• DOI: 10.1007/s00210-023-02553-y

Lung cancer (LC) is the leading cause of cancer-related deaths globally. It accounts for more than 1.9 million cases each year due to its complex and poorly understood molecular mechanisms that result in unregulated cell proliferation and metastasis. β-Catenin is a developmentally active protein that controls cell proliferation, metastasis, polarity and cell fate during homeostasis and aids in cancer progression via epithelial–mesenchymal transition. Therefore, inhibition of the β-catenin pathway could attenuate the progression of LC. Berberine, an isoquinoline alkaloid which is known for its anti-cancer and anti-inflammatory properties, demonstrates poor solubility and bioavailability. In our study, we have encapsulated berberine into liquid crystalline nanoparticles to improve its physiochemical functions and studied if these nanoparticles target the β-catenin pathway to inhibit the human lung adenocarcinoma cell line (A549) at both gene and protein levels. We observed for the first time that berberine liquid crystalline nanoparticles at 5 µM significantly attenuate the expression of the β-catenin gene and protein. The interaction between berberine and β-catenin was further validated by molecular simulation studies. Targeting β-catenin with berberine nanoparticles represents a promising strategy for the management of lung cancer progression.