Onset of p53/NF-κB signaling crosstalk in human melanoma cells in response to anti-cancer theabrownin

Publication type:
Journal article
Metadata:
Autoren
  • Ting Li
  • Bo Yan
  • Xiujuan Xiao
  • Li Zhou
  • Jin Zhang
  • Qiang Yuan
  • Letian Shan
  • Huiling Wu
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000819996500001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1096/fj.202200261R
eISSN
1530-6860
Externe Identifier
  • Clarivate Analytics Document Solution ID: 2P8PV
  • PubMed Identifier: 35779042
ISSN
0892-6638
Ausgabe der Veröffentlichung
8
Zeitschrift
FASEB JOURNAL
Schlüsselwörter
  • crosstalk
  • DNA damage
  • melanoma
  • senescence
  • theabrownin
  • zebrafish
Artikelnummer
ARTN e22426
Datum der Veröffentlichung
2022
Status
Published
Titel
Onset of p53/NF-κB signaling crosstalk in human melanoma cells in response to anti-cancer theabrownin
Sub types
  • Article
Ausgabe der Zeitschrift
36

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Ting Li
  • Bo Yan
  • Xiujuan Xiao
  • Li Zhou
  • Jin Zhang
  • Qiang Yuan
  • Letian Shan
  • Huiling Wu
  • Thomas Efferth
DOI
10.1096/fj.202200261r
eISSN
1530-6860
ISSN
0892-6638
Ausgabe der Veröffentlichung
8
Zeitschrift
The FASEB Journal
Sprache
en
Online publication date
2022
Datum der Veröffentlichung
2022
Status
Published
Herausgeber
Wiley
Herausgeber URL
http://dx.doi.org/10.1096/fj.202200261r
Datum der Datenerfassung
2022
Titel
Onset of p53/ <scp>NF‐κB</scp> signaling crosstalk in human melanoma cells in response to anti‐cancer theabrownin
Ausgabe der Zeitschrift
36

Data source: Crossref

Abstract
As a major tea component, theabrownin represents a promising anti-cancer candidate. However, its effect on the melanoma is unknown. To evaluate the in vitro and in vivo anti-melanoma efficacy of TB, we conducted cell viability, immunostaining, comet, and TUNEL assays on human A375 melanoma cells, and employed a zebrafish xenograft model of A375 cells. Real-time PCR (qPCR) and western blot were conducted to explore the molecular mechanisms of TB. In vitro, TB significantly inhibited the proliferation of A375 cells, and A375 cells showed the highest inhibitory rate among the other melanoma cell line (A875) and human dermal fibroblasts. TB triggered DNA damage and induced apoptosis of A375 cells and significantly inhibited the growth of A375 xenograft tumors in zebrafishes. Several key molecular events were activated by TB, including DNA damage-associated p53 and NF-κB pathways, through up-regulation of GADD45α, γ-H2A.X, phospho-ATM(p-ATM), phospho-ATR (p-ATR), phospho-p53 (p-p53), phospho-IKKα/β (p-IKKα/β), phospho-p65 (p-p65), etc. However, the TB-activated molecular events were counteracted by either knockdown of p53 or p65, and only dual knockdown of both p53 and p65 completed counteracted the anti-melanoma efficacy of TB. In conclusion, TB triggered DNA damage and thereby inhibited proliferation and induced cellular senescence and apoptosis of melanoma cells through mechanisms mediated by p53/NF-κB signaling crosstalk. This is the first report on the efficacy and mechanisms of TB on melanoma cells, making TB a promising candidate for anti-melanoma agent development.
Addresses
  • The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Autoren
  • Ting Li
  • Bo Yan
  • Xiujuan Xiao
  • Li Zhou
  • Jin Zhang
  • Qiang Yuan
  • Letian Shan
  • Huiling Wu
  • Thomas Efferth
DOI
10.1096/fj.202200261r
eISSN
1530-6860
Externe Identifier
  • PubMed Identifier: 35779042
Funding acknowledgements
  • Natural Science Foundation of Zhejiang Province: LY18H270004
  • National Natural Science Foundation of China: 81774331
  • Natural Science Foundation of Zhejiang Province: LQ20H150008
  • National Natural Science Foundation of China: 81873049
Open access
false
ISSN
0892-6638
Ausgabe der Veröffentlichung
8
Zeitschrift
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Schlüsselwörter
  • Animals
  • Zebrafish
  • Humans
  • Melanoma
  • Catechin
  • NF-kappa B
  • Signal Transduction
  • Apoptosis
  • Tumor Suppressor Protein p53
  • I-kappa B Kinase
Sprache
eng
Medium
Print
Paginierung
e22426
Datum der Veröffentlichung
2022
Status
Published
Datum der Datenerfassung
2022
Titel
Onset of p53/NF-κB signaling crosstalk in human melanoma cells in response to anti-cancer theabrownin.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
36

Data source: Europe PubMed Central

Abstract
As a major tea component, theabrownin represents a promising anti-cancer candidate. However, its effect on the melanoma is unknown. To evaluate the in vitro and in vivo anti-melanoma efficacy of TB, we conducted cell viability, immunostaining, comet, and TUNEL assays on human A375 melanoma cells, and employed a zebrafish xenograft model of A375 cells. Real-time PCR (qPCR) and western blot were conducted to explore the molecular mechanisms of TB. In vitro, TB significantly inhibited the proliferation of A375 cells, and A375 cells showed the highest inhibitory rate among the other melanoma cell line (A875) and human dermal fibroblasts. TB triggered DNA damage and induced apoptosis of A375 cells and significantly inhibited the growth of A375 xenograft tumors in zebrafishes. Several key molecular events were activated by TB, including DNA damage-associated p53 and NF-κB pathways, through up-regulation of GADD45α, γ-H2A.X, phospho-ATM(p-ATM), phospho-ATR (p-ATR), phospho-p53 (p-p53), phospho-IKKα/β (p-IKKα/β), phospho-p65 (p-p65), etc. However, the TB-activated molecular events were counteracted by either knockdown of p53 or p65, and only dual knockdown of both p53 and p65 completed counteracted the anti-melanoma efficacy of TB. In conclusion, TB triggered DNA damage and thereby inhibited proliferation and induced cellular senescence and apoptosis of melanoma cells through mechanisms mediated by p53/NF-κB signaling crosstalk. This is the first report on the efficacy and mechanisms of TB on melanoma cells, making TB a promising candidate for anti-melanoma agent development.
Date of acceptance
2022
Autoren
  • Ting Li
  • Bo Yan
  • Xiujuan Xiao
  • Li Zhou
  • Jin Zhang
  • Qiang Yuan
  • Letian Shan
  • Huiling Wu
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/35779042
DOI
10.1096/fj.202200261R
eISSN
1530-6860
Ausgabe der Veröffentlichung
8
Zeitschrift
FASEB J
Schlüsselwörter
  • DNA damage
  • crosstalk
  • melanoma
  • senescence
  • theabrownin
  • zebrafish
  • Animals
  • Apoptosis
  • Catechin
  • Humans
  • I-kappa B Kinase
  • Melanoma
  • NF-kappa B
  • Signal Transduction
  • Tumor Suppressor Protein p53
  • Zebrafish
Sprache
eng
Country
United States
Paginierung
e22426
Datum der Veröffentlichung
2022
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Titel
Onset of p53/NF-κB signaling crosstalk in human melanoma cells in response to anti-cancer theabrownin.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
36

Data source: PubMed

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