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

Author:

Malyla Vamshikrishna,De Rubis Gabriele,Paudel Keshav Raj,Chellappan Dinesh Kumar,Hansbro Nicole G.,Hansbro Philip M.,Dua Kamal

Abstract

Abstract 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.

Funder

university of technology sydney

National Health and Medical Research Council

Cancer Council NSW

Rebecca L. Cooper Medical Research Foundation

Maridulu Budyari Gumal - Sydney Partnership for Health Education, Research and Enterprise

University of Technology Sydney

Publisher

Springer Science and Business Media LLC

Subject

Pharmacology,General Medicine

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