Constitutive activation of the Wnt signaling pathway byCTNNB1 (?-catenin) mutations in a subset of human lung adenocarcinoma

Ostruthin (6-geranyl-7-hydroxycoumarin) is one of the constituents isolated from Paramignya trimera and has been classified as a simple coumarin. We recently reported the synthesis of alkyl triphenylphosphonium (TPP) derivatives from ostruthin and evaluated their anticancer activities. In the present study, we demonstrated that alkyl TPP ostruthin derivatives inhibited the up-regulation of cell-surface intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells stimulated with tumor necrosis factor-α (TNF-α) without affecting cell viability, while ostruthin itself exerted cytotoxicity against A549 cells. The heptyl TPP ostruthin derivative (termed OS8) attenuated the up-regulation of ICAM-1 mRNA expression at concentrations higher than 40 µM in TNF-α-stimulated A549 cells. OS8 inhibited TNF-α-induced nuclear factor κB (NF-κB)-responsive luciferase reporter activity at concentrations higher than 40 µM, but did not affect the translocation of the NF-κB subunit RelA in response to the TNF-α stimulation at concentrations up to 100 µM. A chromatin immunoprecipitation assay showed that OS8 at 100 µM prevented the binding of RelA to the ICAM-1 promoter. We also showed that OS8 at 100 µM inhibited the TNF-α-induced phosphorylation of RelA at Ser 536. Moreover, the TNF-α-induced phosphorylation of an inhibitor of NF-κB α and extracellular signal-regulated kinase was reduced by OS8. These results indicate that OS8 has potential as an anti-inflammatory agent that targets the NF-κB signaling pathway.

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Tualang honey inhibits cell proliferation and promotes apoptosis of human lung adenocarcinoma cells via apoptosis signaling pathway

European Journal of Integrative Medicine ◽

10.1016/j.eujim.2020.101149 ◽

2020 ◽

Vol 37 ◽

pp. 101149

Author(s):

Nazirah Amran ◽

Wan Izlina Wan-Ibrahim ◽

Nurshamimi Nor Rashid ◽

Johari Mohd Ali ◽

Puteri Shafinaz Abdul-Rahman

Keyword(s):

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Signaling Pathway ◽

Human Lung ◽

Human Lung Adenocarcinoma ◽

Adenocarcinoma Cells ◽

Human Lung Adenocarcinoma Cells ◽

Lung Adenocarcinoma Cells ◽

Tualang Honey

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Reverse Regulation Between sFRP 5 and Dkk 1 Gene in Early Stage Lung Adenocancer

10.21203/rs.3.rs-434159/v1 ◽

2021 ◽

Author(s):

Arife Zeybek ◽

Necdet Oz ◽

Serdar Kalemci ◽

Kursad Tosun ◽

Tuba Gökdoğan Edgünlü ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Wnt Signaling ◽

Signaling Pathway ◽

Tumor Tissue ◽

Early Stage ◽

Wnt Signaling Pathway ◽

Normal Lung ◽

Pcr Analysis ◽

Related Protein ◽

Expression Levels

Abstract Purpose: We aimed to examine the expression levels of the genes of APC (Adenomatous Polyposis Coli) 1, APC 2, Dkk (Dickkopf related protein) 1, Dkk -3, sFRP (Secreted frizzled-related protein) -2, sFRP-4, and sFRP-5 genes which play a role in the Wnt signaling pathway in lung adenocarcinoma and adjacent normal lung tissues, and to evaluate their relationship with clinical-pathological factors.Materials and methods: Between 2011 and 2018, the expression levels of the relevant genes in formalin-fixed paraffin-embedded tumor and adjacent intact lung tissue samples of 57 patients who were operated for lung adenocarcinoma were determined by Real-time PCR analysis. Results: The expression levels of the Dkk-1 gene in the tumor tissue, especially in stage I-II, were statistically significantly suppressed compared to normal tissue (p <0.025 ). Although Dkk-1 gene expression was suppressed in the tumor tissue of patients with early-stage lung adenocarcinoma, the level of expression of the sFRP-5 gene was found to be statistically significantly higher (p<0.039). Conclusion: In our study, between the sFRP-5 and Dkk-1 genes, known as the extracellular antagonist of the Wnt signaling pathway was found the reverse regulation. sFRP-5 gene was found as having an oncogenic role in adenocarcinoma development. Reverse regulation between these genes in early-stage lung adenocarcinoma may shed light on the mechanisms associated with the development of carcinogenesis. For that reason, clinically, this relationship needs to research in a larger series of pure adenocarcinoma and normal human lung tissues, separated by its stage, for potential therapeutic target or prognostic its significance.

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