Green tea-derived theabrownin induces cellular senescence and apoptosis of hepatocellular carcinoma through p53 signaling activation and bypassed JNK signaling suppression
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Jiaan Xu
- Xiujuan Xiao
- Bo Yan
- Qiang Yuan
- Xiaoqiao Dong
- Quan Du
- Jin Zhang
- Letian Shan
- Zhishan Ding
- Li Zhou
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000749213300001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1186/s12935-022-02468-3
- eISSN
- 1475-2867
- Externe Identifier
- Clarivate Analytics Document Solution ID: YQ3LH
- PubMed Identifier: 35078476
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- CANCER CELL INTERNATIONAL
- Schlüsselwörter
- Theabrownin
- Hepatocellular carcinoma
- Cellular senescence
- Apoptosis
- p53
- JNK
- SK-Hep-1
- Artikelnummer
- ARTN 39
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Titel
- Green tea-derived theabrownin induces cellular senescence and apoptosis of hepatocellular carcinoma through p53 signaling activation and bypassed JNK signaling suppression
- Sub types
- Article
- Ausgabe der Zeitschrift
- 22
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Theabrownin (TB) is a bioactive component of tea and has been reported to exert effects against many human cancers, but its efficacy and mechanism on hepatocellular carcinoma (HCC) with different p53 genotypes remains unclarified.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>MTT assay, DAPI staining, flow cytometry and SA-β-gal staining were applied to evaluate the effects of TB on HCC cells. Quantitative real time PCR (qPCR) and Western blot (WB) were conducted to explore the molecular mechanism of TB. A xenograft model of zebrafish was established to evaluate the anti-tumor effect of TB.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>MTT assays showed that TB significantly inhibited the proliferation of SK-Hep-1, HepG2, and Huh7 cells in a dose-dependent manner, of which SK-Hep-1 was the most sensitive one with the lowest IC<jats:sub>50</jats:sub> values. The animal data showed that TB remarkably suppressed SK-Hep-1 tumor growth in xenograft model of zebrafish. The cellular data showed TB's pro-apoptotic and pro-senescent effect on SK-Hep-1 cells. The molecular results revealed the mechanism of TB that p53 signaling pathway (p-ATM, p-ATR, γ-H2AX, p-Chk2, and p-p53) was activated with up-regulation of downstream senescent genes (<jats:italic>P16</jats:italic>, <jats:italic>P21</jats:italic>, <jats:italic>IL-6</jats:italic> and <jats:italic>IL-8</jats:italic>) as well as apoptotic genes (<jats:italic>Bim</jats:italic>, <jats:italic>Bax</jats:italic> and <jats:italic>PUMA</jats:italic>) and proteins (Bax, c-Casp9 and c-PARP). The p53-mediated mechanism was verified by using p53-siRNA. Moreover, by using JNK-siRNA, we found JNK as a bypass regulator in TB's mechanism.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>To sum up, TB exerted tumor-inhibitory, pro-senescent and pro-apoptotic effects on SK-Hep-1 cells through ATM-Chk2-p53 signaling axis in accompany with JNK bypass regulation. This is the first report on the pro-senescent effect and multi-target (p53 and JNK) mechanism of TB on HCC cells, providing new insights into the underlying mechanisms of TB's anti-HCC efficacy.</jats:p> </jats:sec>
- Autoren
- Jiaan Xu
- Xiujuan Xiao
- Bo Yan
- Qiang Yuan
- Xiaoqiao Dong
- Quan Du
- Jin Zhang
- Letian Shan
- Zhishan Ding
- Li Zhou
- Thomas Efferth
- DOI
- 10.1186/s12935-022-02468-3
- eISSN
- 1475-2867
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Cancer Cell International
- Sprache
- en
- Artikelnummer
- 39
- Online publication date
- 2022
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1186/s12935-022-02468-3
- Datum der Datenerfassung
- 2022
- Titel
- Green tea-derived theabrownin induces cellular senescence and apoptosis of hepatocellular carcinoma through p53 signaling activation and bypassed JNK signaling suppression
- Ausgabe der Zeitschrift
- 22
Data source: Crossref
- Abstract
- <h4>Background</h4>Theabrownin (TB) is a bioactive component of tea and has been reported to exert effects against many human cancers, but its efficacy and mechanism on hepatocellular carcinoma (HCC) with different p53 genotypes remains unclarified.<h4>Methods</h4>MTT assay, DAPI staining, flow cytometry and SA-β-gal staining were applied to evaluate the effects of TB on HCC cells. Quantitative real time PCR (qPCR) and Western blot (WB) were conducted to explore the molecular mechanism of TB. A xenograft model of zebrafish was established to evaluate the anti-tumor effect of TB.<h4>Results</h4>MTT assays showed that TB significantly inhibited the proliferation of SK-Hep-1, HepG2, and Huh7 cells in a dose-dependent manner, of which SK-Hep-1 was the most sensitive one with the lowest IC<sub>50</sub> values. The animal data showed that TB remarkably suppressed SK-Hep-1 tumor growth in xenograft model of zebrafish. The cellular data showed TB's pro-apoptotic and pro-senescent effect on SK-Hep-1 cells. The molecular results revealed the mechanism of TB that p53 signaling pathway (p-ATM, p-ATR, γ-H2AX, p-Chk2, and p-p53) was activated with up-regulation of downstream senescent genes (P16, P21, IL-6 and IL-8) as well as apoptotic genes (Bim, Bax and PUMA) and proteins (Bax, c-Casp9 and c-PARP). The p53-mediated mechanism was verified by using p53-siRNA. Moreover, by using JNK-siRNA, we found JNK as a bypass regulator in TB's mechanism.<h4>Conclusions</h4>To sum up, TB exerted tumor-inhibitory, pro-senescent and pro-apoptotic effects on SK-Hep-1 cells through ATM-Chk2-p53 signaling axis in accompany with JNK bypass regulation. This is the first report on the pro-senescent effect and multi-target (p53 and JNK) mechanism of TB on HCC cells, providing new insights into the underlying mechanisms of TB's anti-HCC efficacy.
- Addresses
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
- Autoren
- Jiaan Xu
- Xiujuan Xiao
- Bo Yan
- Qiang Yuan
- Xiaoqiao Dong
- Quan Du
- Jin Zhang
- Letian Shan
- Zhishan Ding
- Li Zhou
- Thomas Efferth
- DOI
- 10.1186/s12935-022-02468-3
- eISSN
- 1475-2867
- Externe Identifier
- PubMed Identifier: 35078476
- PubMed Central ID: PMC8788116
- Funding acknowledgements
- National Natural Science Foundation of China: 82074464
- National Natural Science Foundation of China: 81873049
- Natural Science Foundation of Zhejiang Province: LY18H270016
- Natural Science Foundation of Zhejiang Province: LY18H270004
- Open access
- true
- ISSN
- 1475-2867
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Cancer cell international
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2022
- Open access status
- Open Access
- Paginierung
- 39
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2022
- Titel
- Green tea-derived theabrownin induces cellular senescence and apoptosis of hepatocellular carcinoma through p53 signaling activation and bypassed JNK signaling suppression.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 22
Files
https://cancerci.biomedcentral.com/counter/pdf/10.1186/s12935-022-02468-3 https://europepmc.org/articles/PMC8788116?pdf=render
Data source: Europe PubMed Central
- Abstract
- BACKGROUND: Theabrownin (TB) is a bioactive component of tea and has been reported to exert effects against many human cancers, but its efficacy and mechanism on hepatocellular carcinoma (HCC) with different p53 genotypes remains unclarified. METHODS: MTT assay, DAPI staining, flow cytometry and SA-β-gal staining were applied to evaluate the effects of TB on HCC cells. Quantitative real time PCR (qPCR) and Western blot (WB) were conducted to explore the molecular mechanism of TB. A xenograft model of zebrafish was established to evaluate the anti-tumor effect of TB. RESULTS: MTT assays showed that TB significantly inhibited the proliferation of SK-Hep-1, HepG2, and Huh7 cells in a dose-dependent manner, of which SK-Hep-1 was the most sensitive one with the lowest IC50 values. The animal data showed that TB remarkably suppressed SK-Hep-1 tumor growth in xenograft model of zebrafish. The cellular data showed TB's pro-apoptotic and pro-senescent effect on SK-Hep-1 cells. The molecular results revealed the mechanism of TB that p53 signaling pathway (p-ATM, p-ATR, γ-H2AX, p-Chk2, and p-p53) was activated with up-regulation of downstream senescent genes (P16, P21, IL-6 and IL-8) as well as apoptotic genes (Bim, Bax and PUMA) and proteins (Bax, c-Casp9 and c-PARP). The p53-mediated mechanism was verified by using p53-siRNA. Moreover, by using JNK-siRNA, we found JNK as a bypass regulator in TB's mechanism. CONCLUSIONS: To sum up, TB exerted tumor-inhibitory, pro-senescent and pro-apoptotic effects on SK-Hep-1 cells through ATM-Chk2-p53 signaling axis in accompany with JNK bypass regulation. This is the first report on the pro-senescent effect and multi-target (p53 and JNK) mechanism of TB on HCC cells, providing new insights into the underlying mechanisms of TB's anti-HCC efficacy.
- Date of acceptance
- 2022
- Autoren
- Jiaan Xu
- Xiujuan Xiao
- Bo Yan
- Qiang Yuan
- Xiaoqiao Dong
- Quan Du
- Jin Zhang
- Letian Shan
- Zhishan Ding
- Li Zhou
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/35078476
- DOI
- 10.1186/s12935-022-02468-3
- Externe Identifier
- PubMed Central ID: PMC8788116
- Funding acknowledgements
- National Natural Science Foundation of China: 81873049
- National Natural Science Foundation of China: 82074464
- Natural Science Foundation of Zhejiang Province: LY18H270016
- Natural Science Foundation of Zhejiang Province: LY18H270004
- ISSN
- 1475-2867
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Cancer Cell Int
- Schlüsselwörter
- Apoptosis
- Cellular senescence
- Hepatocellular carcinoma
- JNK
- SK-Hep-1
- Theabrownin
- p53
- Sprache
- eng
- Country
- England
- Paginierung
- 39
- PII
- 10.1186/s12935-022-02468-3
- Datum der Veröffentlichung
- 2022
- Status
- Published online
- Titel
- Green tea-derived theabrownin induces cellular senescence and apoptosis of hepatocellular carcinoma through p53 signaling activation and bypassed JNK signaling suppression.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 22
Data source: PubMed
- Beziehungen:
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