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

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.

The Nexus of Inflammation-Induced Epithelial-Mesenchymal Transition and Lung Cancer Progression: A Roadmap to Pentacyclic Triterpenoid-Based Therapies

“…Natural metabolites represent an important source of drug candidates with pronounced anti-inflammatory and anti-tumor properties [10]. These compounds can be considered effective inhibitors of the EMT in lung cancer cells, as has already been shown for lignans (arctigenin [136]), alkaloids (berberine [137]), flavonoids (luteolin [138]), phenolic compounds (eugenol [139]), resveratrol [140], curcumin [141]), and other molecules (more details on this topic can be found in the following recently published comprehensive reviews [142][143][144]). Given the lack of reviews analyzing in detail the bioactivity of pentacyclic triterpenoids (PTs) against the links between inflammation and EMT, this chapter will focus on this class of natural compounds.…”

Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer

“…The physiochemical functions of berberine can be largely improved by being encapsulated into liquid crystalline nanoparticles. Berberine liquid crystalline nanoparticles significantly suppresses the expression of β-catenin at both transcription and translation level [ 254 ].…”

The development of nanocarriers for natural products

“…In addition, Malyla et al employed liquid crystal NPs to encapsulate berberine through the ultrasonication technique, improving the bioavailability, stability, and sustained release properties of berberine. Their in vitro experiments indicated that the nano‐encapsulated berberine markedly downregulated β‐catenin expression at both the gene and protein levels, effectively inhibiting the proliferation of the human lung adenocarcinoma cell line A549 (Malyla et al, 2023).…”