Green tea-derived theabrownin suppresses human non-small cell lung carcinoma in xenograft model through activation of not only p53 signaling but also MAPK/JNK signaling pathway
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Xiujuan Xiao
- Le Guo
- Weiyou Dai
- Bo Yan
- Jin Zhang
- Qiang Yuan
- Li Zhou
- Letian Shan
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000793246200005&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.jep.2022.115167
- eISSN
- 1872-7573
- Externe Identifier
- Clarivate Analytics Document Solution ID: 1C6SL
- PubMed Identifier: 35271947
- ISSN
- 0378-8741
- Zeitschrift
- JOURNAL OF ETHNOPHARMACOLOGY
- Schlüsselwörter
- Theabrownin
- NSCLC
- Larval zebrafish
- JNK
- Apoptosis
- Migration
- Artikelnummer
- ARTN 115167
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Titel
- Green tea-derived theabrownin suppresses human non-small cell lung carcinoma in xenograft model through activation of not only p53 signaling but also MAPK/JNK signaling pathway
- Sub types
- Article
- Ausgabe der Zeitschrift
- 291
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Xiujuan Xiao
- Le Guo
- Weiyou Dai
- Bo Yan
- Jin Zhang
- Qiang Yuan
- Li Zhou
- Letian Shan
- Thomas Efferth
- DOI
- 10.1016/j.jep.2022.115167
- ISSN
- 0378-8741
- Zeitschrift
- Journal of Ethnopharmacology
- Sprache
- en
- Artikelnummer
- 115167
- Paginierung
- 115167 - 115167
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.jep.2022.115167
- Datum der Datenerfassung
- 2023
- Titel
- Green tea-derived theabrownin suppresses human non-small cell lung carcinoma in xenograft model through activation of not only p53 signaling but also MAPK/JNK signaling pathway
- Ausgabe der Zeitschrift
- 291
Data source: Crossref
- Abstract
- <h4>Ethnopharmacological relevance</h4>According to the theory and practice of traditional Chinese medicine (TCM), the pathogenesis of lung carcinoma is associated with many syndromes, such as "sputum stasis", "cough", "lung fever", "lung toxin", and "hemoptysis", which should be removed for therapeutic purpose. Tea is not only a world-wide beverage, but also a TCM herb, possessing activities against the above syndromes. Recently, green tea extract exerted inhibitory effects on a variety of tumor cells. As a pigment active substance of green tea, theabrownin (TB) has been found to inhibit many cancer cells.<h4>Aim of the study</h4>This study focused on the efficacy and mechanism of TB on non-small cell lung cancer (NSCLC) cell lines. The in vivo efficacy of TB on p53-deficient NSCLC (H1299) cells and p53-wild type NSCLC (A549) cells NSCLC cells were determined, and its mechanism of action was explored.<h4>Materials and methods</h4>In vivo, two lung cancer cell lines, H1299 (p53-deficient) and A549 (p53-wild type) were selected to establish xenograft models of larval zebrafish, respectively. For in vitro experiments, wound healing assay, DAPI staining, TUNEL assay, immunofluorescence assay, and flow cytometry were conducted in these two cell lines. RNA sequencing (RNAseq), real time PCR (qPCR) and Western blot (WB) were performed for the mechanism study.<h4>Results</h4>The in vivo results showed that TB significantly inhibited the H1299 and the A549 xenograft tumor growth in larval zebrafish (dosage ranged from 2.13 to 21.3 μg/ml). Wound healing assay results showed that TB suppressed the migration of H1299 cells. DAPI staining, TUNEL assay, and immunofluorescence assay results showed that TB inhibited the growth of H1299 cells by inducing apoptosis. RNAseq, qPCR and WB data showed that TB significantly up-regulated the MAPK/JNK pathway-related proteins (ASK-1, JNK and c-JUN) through phosphorylation activation, accompanying with down-regulation of the epithelial-mesenchymal transition (EMT)-associated genes (N-CADHERIN, SLUG, FIBROWNECTIN and ZEB1) and anti-apoptotic molecules (BCL-2), and up-regulation of the metastasis-related gene HSPA6 and the pro-apoptotic molecules (BIM, BAX, PARP, c-PARP, γ-H2A.X, c-CASP3, c-CASP8, c-CASP9, DDIT3 and DUSP8).<h4>Conclusion</h4>This study determined the in vivo efficacy of green tea-derived TB on p53-deficient NSCLC (H1299) cells and p53-wild type NSCLC (A549) cells and clarified its p53-independent mechanism mediated by the activation of MAPK/JNK signaling pathway.
- Addresses
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China; The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
- Autoren
- Xiujuan Xiao
- Le Guo
- Weiyou Dai
- Bo Yan
- Jin Zhang
- Qiang Yuan
- Li Zhou
- Letian Shan
- Thomas Efferth
- DOI
- 10.1016/j.jep.2022.115167
- eISSN
- 1872-7573
- Externe Identifier
- PubMed Identifier: 35271947
- Open access
- false
- ISSN
- 0378-8741
- Zeitschrift
- Journal of ethnopharmacology
- Schlüsselwörter
- Cell Line, Tumor
- Animals
- Zebrafish
- Humans
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
- Catechin
- Apoptosis
- Cell Proliferation
- Cell Movement
- MAP Kinase Signaling System
- Tea
- Tumor Suppressor Protein p53
- Heterografts
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2022
- Paginierung
- 115167
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum der Datenerfassung
- 2022
- Titel
- Green tea-derived theabrownin suppresses human non-small cell lung carcinoma in xenograft model through activation of not only p53 signaling but also MAPK/JNK signaling pathway.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 291
Data source: Europe PubMed Central
- Abstract
- ETHNOPHARMACOLOGICAL RELEVANCE: According to the theory and practice of traditional Chinese medicine (TCM), the pathogenesis of lung carcinoma is associated with many syndromes, such as "sputum stasis", "cough", "lung fever", "lung toxin", and "hemoptysis", which should be removed for therapeutic purpose. Tea is not only a world-wide beverage, but also a TCM herb, possessing activities against the above syndromes. Recently, green tea extract exerted inhibitory effects on a variety of tumor cells. As a pigment active substance of green tea, theabrownin (TB) has been found to inhibit many cancer cells. AIM OF THE STUDY: This study focused on the efficacy and mechanism of TB on non-small cell lung cancer (NSCLC) cell lines. The in vivo efficacy of TB on p53-deficient NSCLC (H1299) cells and p53-wild type NSCLC (A549) cells NSCLC cells were determined, and its mechanism of action was explored. MATERIALS AND METHODS: In vivo, two lung cancer cell lines, H1299 (p53-deficient) and A549 (p53-wild type) were selected to establish xenograft models of larval zebrafish, respectively. For in vitro experiments, wound healing assay, DAPI staining, TUNEL assay, immunofluorescence assay, and flow cytometry were conducted in these two cell lines. RNA sequencing (RNAseq), real time PCR (qPCR) and Western blot (WB) were performed for the mechanism study. RESULTS: The in vivo results showed that TB significantly inhibited the H1299 and the A549 xenograft tumor growth in larval zebrafish (dosage ranged from 2.13 to 21.3 μg/ml). Wound healing assay results showed that TB suppressed the migration of H1299 cells. DAPI staining, TUNEL assay, and immunofluorescence assay results showed that TB inhibited the growth of H1299 cells by inducing apoptosis. RNAseq, qPCR and WB data showed that TB significantly up-regulated the MAPK/JNK pathway-related proteins (ASK-1, JNK and c-JUN) through phosphorylation activation, accompanying with down-regulation of the epithelial-mesenchymal transition (EMT)-associated genes (N-CADHERIN, SLUG, FIBROWNECTIN and ZEB1) and anti-apoptotic molecules (BCL-2), and up-regulation of the metastasis-related gene HSPA6 and the pro-apoptotic molecules (BIM, BAX, PARP, c-PARP, γ-H2A.X, c-CASP3, c-CASP8, c-CASP9, DDIT3 and DUSP8). CONCLUSION: This study determined the in vivo efficacy of green tea-derived TB on p53-deficient NSCLC (H1299) cells and p53-wild type NSCLC (A549) cells and clarified its p53-independent mechanism mediated by the activation of MAPK/JNK signaling pathway.
- Date of acceptance
- 2022
- Autoren
- Xiujuan Xiao
- Le Guo
- Weiyou Dai
- Bo Yan
- Jin Zhang
- Qiang Yuan
- Li Zhou
- Letian Shan
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/35271947
- DOI
- 10.1016/j.jep.2022.115167
- eISSN
- 1872-7573
- Zeitschrift
- J Ethnopharmacol
- Schlüsselwörter
- Apoptosis
- JNK
- Larval zebrafish
- Migration
- NSCLC
- Theabrownin
- Animals
- Apoptosis
- Carcinoma, Non-Small-Cell Lung
- Catechin
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Heterografts
- Humans
- Lung Neoplasms
- MAP Kinase Signaling System
- Tea
- Tumor Suppressor Protein p53
- Zebrafish
- Sprache
- eng
- Country
- Ireland
- Paginierung
- 115167
- PII
- S0378-8741(22)00205-7
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2022
- Titel
- Green tea-derived theabrownin suppresses human non-small cell lung carcinoma in xenograft model through activation of not only p53 signaling but also MAPK/JNK signaling pathway.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 291
Data source: PubMed
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