Theanine from tea and its semi-synthetic derivative TBrC suppress human cervical cancer growth and migration by inhibiting EGFR/Met-Akt/NF-κB signaling

Liu, Jiannan; Sun, Yehuan; Zhang, Huarong; Ji, Dexin; Wu, Fei; Tian, Huihui; Liu, Kun; Zhang, Ying; Wu, Benhao; Zhang, Guoying

doi:10.1016/j.ejphar.2016.09.007

Cited by 30 publications

(50 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been found that MAPK and NF-κB are the upstream signaling molecules of C-MYC , activation of which positively correlates with c-myc-mediated cell proliferation and cell cycle progression in lung cancer ( Tang et al, 2013 ; Lim et al, 2016 ). Other publications reported that tea and its components could inhibit human cell growth and migration by inhibiting MAPK or NF-κB signaling ( Karki et al, 2011 ; Liu et al, 2016 ; Zhou et al, 2016 ), suggesting the potential importance of those signaling molecules in the role of TB. Therefore, more studies in future are needed to explore MAPK and NF-κB signaling pathways in the c-myc-related mechanism of TB.…”

Section: Discussionmentioning

confidence: 99%

Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism

Zhou

Wu²,

Jin

et al. 2017

Front. Pharmacol.

View full text Add to dashboard Cite

Green tea, the fresh leaves of Camellia sinensis, is not only a health-promoting beverage but also a traditional Chinese medicine used for prevention or treatment of cancer, such as lung cancer. Theabrownin (TB) is the main fraction responsible for the medicinal effects of green tea, but whether it possesses anti-cancer effect is unknown yet. This study aimed to determine the in vitro and in vivo anti-lung cancer effect of TB and explore the underlying molecular mechanism, by using A549 cell line and Lewis lung carcinoma-bearing mice. In cellular experiment, MTT assay was performed to evaluate the inhibitory effect and IC50 values of TB, and flow cytometry was conducted to analyze the cell cycle progression affected by TB. In animal experiment, mice body mass, tumor incidence, tumor size and tumor weight were measured, and histopathological analysis on tumor was performed with Transferase dUTP nick-end labeling staining. Real time PCR and western blot assays were adopted to detect the expression of C-MYC associated genes and proteins for mechanism clarification. TB was found to inhibit A549 cell viability in a dose- and time-dependent manner and block A549 cell cycle at G0/G1 phase. Down-regulation of c-myc, cyclin A, cyclin D, cdk2, cdk4, proliferation of cell nuclear antigen and up-regulation of p21, p27, and phosphate and tension homolog in both gene and protein levels were observed with TB treatment. A c-myc-related mechanism was thereby proposed, since c-myc could transcriptionally regulate all other genes in its downstream region for G1/S transitions of cell cycle and proliferation of cancer cells. This is the first report regarding the anti-NSCLC effect and the underlying mechanism of TB on cell cycle progression and proliferation of A549 cells. The in vivo data verified the in vitro result that TB could significantly inhibit the lung cancer growth in mice and induce apoptosis on tumors in a dose-dependent manner. It provides a promising candidate of natural products for lung cancer therapy and new development of anti-cancer agent.

show abstract

Section: Discussionmentioning

confidence: 99%

Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism

Zhou

Wu²,

Jin

et al. 2017

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Other constituents of green tea, for example, EGCG, have been reported to have OA protective effects in human chondrocytes [ 18 ] and in a post-traumatic OA mouse model [ 19 ]. Biological activities of L-theanine, including anti-inflammatory, antioxidant, anti-tumor, neuroprotective effects, immune regulation [ 20 , 21 , 22 , 23 ], and inhibiting the NF-κB pathway have been observed. However, the role of L-theanine in OA inflammation and whether it can regulate the metabolic activity of chondrocytes are still unclear.…”

Section: Introductionmentioning

confidence: 99%

L-Theanine Reduced the Development of Knee Osteoarthritis in Rats via Its Anti-Inflammation and Anti-Matrix Degradation Actions: In Vivo and In Vitro Study

Bai

Zhang

et al. 2020

Nutrients

View full text Add to dashboard Cite

The etiology of osteoarthritis (OA) is multifactorial, with no effective disease-modifying-drugs. L-theanine has been reported to inhibit inflammatory responses in some diseases and this study aimed to investigate the effect of L-theanine on Interleukin-1(IL-1)β-stimulated chondrocytes, and in an injury-induced OA rat model. Primary chondrocytes were stimulated by IL-1β (10 ng/mL) for 24 h and then co-cultured with L-theanine for 24 h. The effects of L-theanine on IL-1β-stimulated expression of pro-inflammatory cytokines and hydrolytic enzyme were analyzed using Western blotting, quantitative polymerase chain reaction (q-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. An immunofluorescence assay was used to detect nuclear factor kappa B (NF-κB) phosphorylation. OA was induced by anterior cruciate ligament transection (ACLT) surgery in rats and celecoxib was used as a positive control. OA severity was measured using the Osteoarthritis Research Society International (OARSI) grading system to describe histological changes. The results showed that L-theanine decreased the expression of pro-inflammatory mediators, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), both in vivo and in vitro. L-theanine treatment inhibited IL-1β-induced upregulation of matrix metalloproteinases (MMP)-3 and MMP-13, as well as inhibited NF-κB p65 activation. In vivo animal model showed that L-theanine administration (200 mg/kg) significantly alleviated OA lesions and decreased OARSI score. Our data indicated that L-theanine decreased inflammatory cytokines and protected extracellular matrix degradation through inhibition of the NF-κB pathway, and L-theanine may be considered a promising therapeutic strategy in OA prevention.

show abstract

“…Our previous study has demonstrated that the expression of E-cadherin was downregulated and the expression of fibronectin was upregulated in human PCO attached LECs and in the LECs obtained from patients with anterior polar cataracts [ 5 , 6 ]. EGF has previously been demonstrated to regulate MYC and EZH2 expression [ 16 , 17 ]. To explore whether MYC and EZH2 were involved in EGF inducing EMT in primary HLECs, we analyzed the expression levels of MYC mRNA and EZH2 mRNA.…”

Section: Resultsmentioning

confidence: 99%

EGF-Mediated Overexpression of Myc Attenuates miR-26b by Recruiting HDAC3 to Induce Epithelial-Mesenchymal Transition of Lens Epithelial Cells

Dong

2018

BioMed Research International

View full text Add to dashboard Cite

The previous study has demonstrated that epidermal growth factor (EGF) and EGF receptor (EGFR) signaling plays a critical role in the development of posterior capsule opacification (PCO) through regulating lens epithelial cells (LECs) proliferation. Recent studies have suggested that the residual LECs undergo proliferation and migration, and epithelial-mesenchymal transition (EMT) is the important cause of PCO formation after cataract surgery. EMT of LECs is considered to be playing a central role in the pathogenesis of PCO. In the present study, we investigated whether and how EGF may regulate EMT of LECs. First, we demonstrated that EGF and EGFR signaling induces Myc overexpression in primary human lens epithelial cells (HLECs). In turn, Myc overexpression could inhibit miR-26b by recruitment of HDAC3. Consequently, the downregulated expression of miR-26b increased the expression of EZH2 in primary HLECs. Mechanistically, miR-26b directly controls EZH2 expression by targeting its 3′-UTR in HLECs by luciferase reporter assays. Finally, we demonstrated that EGF induces the expression of EMT markers in primary HLECs via a miR-26b-dependent mechanism. In summary, EGF activated Myc and Myc overexpression inhibited miR-26b by recruitment of HDAC3, which in turn induced the expression of EZH2 and promoted the progression of EMT in HLECs.

show abstract

Theanine from tea and its semi-synthetic derivative TBrC suppress human cervical cancer growth and migration by inhibiting EGFR/Met-Akt/NF-κB signaling

Cited by 30 publications

References 30 publications

Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism

Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism

L-Theanine Reduced the Development of Knee Osteoarthritis in Rats via Its Anti-Inflammation and Anti-Matrix Degradation Actions: In Vivo and In Vitro Study

EGF-Mediated Overexpression of Myc Attenuates miR-26b by Recruiting HDAC3 to Induce Epithelial-Mesenchymal Transition of Lens Epithelial Cells

Contact Info

Product

Resources

About