Quercetin Inhibits the Proliferation and Metastasis of Human Non-Small Cell Lung Cancer Cell Line: The Key Role of Src-Mediated Fibroblast Growth Factor-Inducible 14 (Fn14)/ Nuclear Factor kappa B (NF-κB) pathway

Abstract

Departmental sources Background:Quercetin (Que) is reported to induce apoptosis of lung cancer cells. Src is closely related to the progression of non-small cell lung cancer (NSCLC) and can be modulated by Que in macrophages. In the current study, the interaction between Que and Src signaling in NSCLC cells was explored to explain the anti-NSCLC function of Que. Material/Methods: NSCLC cell line HCC827 was subjected to the administrations of Que at different concentrations. The effect of Que on tumor cell proliferation was detected using MTT and colony formation assays. Then the effect on the migration and invasion abilities was assessed using scratch and Transwell assays. At molecular level, the changes in Src/Fn14/NF-kB signaling were determined using western blotting assays. The role of Src in the function of Que was further explored by inducing the expression of Src gene in NSCLC cells before Que administration.The results of the in vitro assays were verified using a NSCLC mice model. Results:Que inhibited the proliferation and anchorage-independent growth of NSCLC cells. Additionally, Que delayed in the gap closure rate in scratch assays and decreased the membrane-penetrating cell number in Transwell assays. At a molecular level, Que suppressed the expression of Src, which subsequently inhibited Fn14/NF-kB signaling. In in vivo assays, Que inhibited the growth of solid tumors. After the overexpression of Src in NSCLC cells, the anti-NSCLC effect of Que was blocked by inducing NSCLC proliferation and metastasis, and by activating Fn14/NF-kB signaling. Moreover, the induced level of Src promoted the growth and metastasis potential of solid tumors in mice. Conclusions:Que exerted the anti-NSCLC effect by inhibiting Src-mediated Fn14/NF-kB pathway both in vitro and in vivo.

Using Network Pharmacology and Molecular Docking to Explore the Mechanism of Shan Ci Gu (Cremastra appendiculata) Against Non-Small Cell Lung Cancer

“…Dong et al found that quercetin inhibited the expression of Src, and subsequently, inhibited Fn14/NF-kappa B signaling, thereby suppressing the proliferation and metastasis of NSCLC. This suggests that Src expression promotes NSCLC progression and could be a target for the treatment of NSCLC ( Dong et al, 2020 ). In the ErbB signaling pathway, the ErbB receptor family and its downstream pathways may regulate epithelial-mesenchymal transition, migration, and tumor invasion by regulating components of the extracellular matrix (ECM) ( Kern et al, 1992 ).…”

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

“…Inhibited cell proliferation and tumor growth [408,411,412]. Delayed appearance of lung adenocarcinoma [420].…”

“…Quercetin dose-dependently suppressed HGF- and TGFα-induced migration of hepatocellular carcinoma cells by inhibiting the signaling pathway of AKT, but not p38 MAPK [ 413 ]. In non-small cell lung carcinoma models, quercetin inhibited proliferation and anchorage-independent growth by inhibiting the Src-mediated Fn14/NF-ĸB pathway both in vitro and in vivo [ 408 ] and improved the radiosensitivity of these cells by altering the expression of miR-16-5p and Wee1 [ 414 ]. In vivo, lung adenocarcinoma appearance was delayed and increased non-neoplastic body weight gain in mice with tumor oxidative stress after daily treatment with quercetin was observed [ 420 ].…”

Potential Therapeutic Targets of Quercetin, a Plant Flavonol, and Its Role in the Therapy of Various Types of Cancer through the Modulation of Various Cell Signaling Pathways

“…An in vivo study showed that Qu injection in A549 tumor-bearing mice efficiently repressed growth of cancer [ 160 ]. Generally, mostly studies on Qu concentrated on its growth inhibitory action through initiation of apoptosis [ 65 ] or autophagy [ 271 ] development of chemosensitivity [ 272 ] and Qu exerted the anti-NSCLC effect by inhibiting Src-mediated Fn14/NF- κ B pathway both in vitro and in vivo [ 273 ].…”