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  1. Fulltext Berberine nanostructures attenuate ß-catenin, a key component of epithelial mesenchymal transition in lung adenocarcinoma
    Malyla V, De Rubis G, Paudel KR, Chellappan DK, Hansbro NG, Hansbro PM, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2023 Dec;396(12):3595-3603.
    PMID: 37266589 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.
    Matched MeSH terms: Catenins/metabolism
  2. Fulltext Triptolide inhibits epithelial-mesenchymal transition phenotype through the p70S6k/GSK3/β-catenin signaling pathway in taxol-resistant human lung adenocarcinoma
    Tian Y, Li P, Xiao Z, Zhou J, Xue X, Jiang N, et al.
    Transl Lung Cancer Res, 2021 Feb;10(2):1007-1019.
    PMID: 33718039 DOI: 10.21037/tlcr-21-145
    Background: Chemotherapy is one of the primary treatments for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), however, chemoresistance develops over time and is a bottleneck to effective chemotherapy worldwide. Therefore, the development of new potent therapeutic agents to overcome chemoresistance is of utmost importance. Triptolide is a natural component extracted from Tripterygium Wilfordii, a Chinese plant; our study aimed to evaluate its anti-tumor effects in taxol-resistant human lung adenocarcinoma and investigate its molecular mechanisms of chemoresistance.

    Methods: Triptolide's inhibition of cell viability was detected by sulforhodamine B (SRB) assay. Cell cycle was measured by flow cytometry and cell apoptosis was assessed by flow cytometry and western blot. Expression of β-catenin was analyzed by western blot and immunofluorescence (IF). The anti-tumor effects of triptolide were determined using a subcutaneous in-vivo model. Cell proliferation and apoptosis were evaluated by immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. The expression level of p-p70S6K and p-GSK-3α/β was evaluated by western blot and IHC.

    Results: Triptolide inhibited cell proliferation, induced S-phase cell cycle arrest and apoptosis in taxol-resistant A549 (A549/TaxR) cells. Moreover, intraperitoneal injection of triptolide resulted in a significant delay of tumor growth without obvious systemic toxicity in mice. Additionally, triptolide reversed epithelial-mesenchymal transition (EMT) through repression of the p70S6K/GSK3/β-catenin signaling pathway.

    Conclusions: Our study provides evidence that triptolide can reverse EMT in taxol-resistant lung adenocarcinoma cells and impairs tumor growth by inhibiting the p70S6K/GSK3/β-catenin pathway, indicating that triptolide has potential to be used as a new therapeutic agent for taxol-resistant lung adenocarcinoma.

    Matched MeSH terms: Catenins
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