Theabrownin triggers DNA damage to suppress human osteosarcoma U2OS cells by activating p53 signalling pathway

Abstract

AbstractOsteosarcoma becomes the second leading cause of cancer death in the younger population. Current outcomes of chemotherapy on osteosarcoma were unsatisfactory to date, demanding development of effective therapies. Tea is a commonly used beverage beneficial to human health. As a major component of tea, theabrownin has been reported to possess anti‐cancer activity. To evaluate its anti‐osteosarcoma effect, we established a xenograft model of zebrafish and employed U2OS cells for in vivo and in vitro assays. The animal data showed that TB significantly inhibited the tumour growth with stronger effect than that of chemotherapy. The cellular data confirmed that TB‐triggered DNA damage and induced apoptosis of U2OS cells by regulation of Mki67, PARP, caspase 3 and H2AX, and Western blot assay showed an activation of p53 signalling pathway. When P53 was knocked down by siRNA, the subsequent downstream signalling was blocked, indicating a p53‐dependent mechanism of TB on U2OS cells (p53 wt). Using osteosarcoma cell lines with p53 mutations (HOS, SAOS‐2 and MG63), we found that TB exerted stronger inhibitory effect on U2OS cells than that on p53‐mut cell lines, but it also exerted obvious effect on SAOS‐2 cells (p53 null), suggesting an activation of p53‐independent pathway in the p53‐null cells. Interestingly, theabrownin was found to have no toxicity on normal tissue in vivo and could even increase the viability of p53‐wt normal cells. In sum, theabrownin could trigger DNA damage and induce apoptosis on U2OS cells via a p53‐dependent mechanism, being a promising candidate for osteosarcoma therapy.

Autoren

Wangdong Jin
Li Zhou
Bo Yan
Li Yan
Fucun Liu
Peijian Tong
Wenhua Yu
Xiaoqiao Dong
Li Xie
Jin Zhang
Yiqiao Xu
Chunqi Li
Qiang Yuan
Letian Shan
Thomas Efferth

DOI

10.1111/jcmm.13742

eISSN

1582-4934

ISSN

1582-1838

Ausgabe der Veröffentlichung

9

Zeitschrift

Journal of Cellular and Molecular Medicine

Sprache

en

Online publication date

2018

Paginierung

4423 - 4436

Datum der Veröffentlichung

2018

Status

Published

Herausgeber

Wiley

Herausgeber URL

http://dx.doi.org/10.1111/jcmm.13742

Datum der Datenerfassung

2023

Titel

Theabrownin triggers <scp>DNA</scp> damage to suppress human osteosarcoma U2<scp>OS</scp> cells by activating p53 signalling pathway

Ausgabe der Zeitschrift

22

Data source: Crossref

Abstract

Osteosarcoma becomes the second leading cause of cancer death in the younger population. Current outcomes of chemotherapy on osteosarcoma were unsatisfactory to date, demanding development of effective therapies. Tea is a commonly used beverage beneficial to human health. As a major component of tea, theabrownin has been reported to possess anti-cancer activity. To evaluate its anti-osteosarcoma effect, we established a xenograft model of zebrafish and employed U2OS cells for in vivo and in vitro assays. The animal data showed that TB significantly inhibited the tumour growth with stronger effect than that of chemotherapy. The cellular data confirmed that TB-triggered DNA damage and induced apoptosis of U2OS cells by regulation of Mki67, PARP, caspase 3 and H2AX, and Western blot assay showed an activation of p53 signalling pathway. When P53 was knocked down by siRNA, the subsequent downstream signalling was blocked, indicating a p53-dependent mechanism of TB on U2OS cells (p53 wt). Using osteosarcoma cell lines with p53 mutations (HOS, SAOS-2 and MG63), we found that TB exerted stronger inhibitory effect on U2OS cells than that on p53-mut cell lines, but it also exerted obvious effect on SAOS-2 cells (p53 null), suggesting an activation of p53-independent pathway in the p53-null cells. Interestingly, theabrownin was found to have no toxicity on normal tissue in vivo and could even increase the viability of p53-wt normal cells. In sum, theabrownin could trigger DNA damage and induce apoptosis on U2OS cells via a p53-dependent mechanism, being a promising candidate for osteosarcoma therapy.

Addresses

The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.

Autoren

Wangdong Jin
Li Zhou
Bo Yan
Li Yan
Fucun Liu
Peijian Tong
Wenhua Yu
Xiaoqiao Dong
Li Xie
Jin Zhang
Yiqiao Xu
Chunqi Li
Qiang Yuan
Letian Shan
Thomas Efferth

DOI

10.1111/jcmm.13742

eISSN

1582-4934

Externe Identifier

PubMed Identifier: 29993186
PubMed Central ID: PMC6111873

Funding acknowledgements

Natural Science Foundation of Zhejiang Province: LY17H270016
National Natural Science Foundation of China: 81673997
Natural Science Foundation of Zhejiang Province: LY16H060005
Natural Science Foundation of Zhejiang Province: LY16H270011
Natural Science Foundation of Zhejiang Province: LY17H270001
National Natural Science Foundation of China: 81774331

Open access

true

ISSN

1582-1838

Ausgabe der Veröffentlichung

9

Zeitschrift

Journal of cellular and molecular medicine

Schlüsselwörter

Cell Line, Tumor
Osteoblasts
Mesenchymal Stem Cells
Animals
Zebrafish
Humans
Osteosarcoma
Bone Neoplasms
DNA Damage
Cisplatin
Catechin
Poly(ADP-ribose) Polymerases
Histones
Ki-67 Antigen
RNA, Small Interfering
Antineoplastic Agents, Phytogenic
Xenograft Model Antitumor Assays
Signal Transduction
Cell Cycle
Apoptosis
Cell Survival
Gene Expression Regulation, Neoplastic
Larva
Tumor Suppressor Protein p53
Caspase 3

Sprache

eng

Medium

Print-Electronic

Online publication date

2018

Open access status

Open Access

Paginierung

4423 - 4436

Datum der Veröffentlichung

2018

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2018

Titel

Theabrownin triggers DNA damage to suppress human osteosarcoma U2OS cells by activating p53 signalling pathway.

Sub types

Research Support, Non-U.S. Gov't
research-article
Journal Article

Ausgabe der Zeitschrift

22

Files

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.13742 https://europepmc.org/articles/PMC6111873?pdf=render

Data source: Europe PubMed Central

Abstract

Osteosarcoma becomes the second leading cause of cancer death in the younger population. Current outcomes of chemotherapy on osteosarcoma were unsatisfactory to date, demanding development of effective therapies. Tea is a commonly used beverage beneficial to human health. As a major component of tea, theabrownin has been reported to possess anti-cancer activity. To evaluate its anti-osteosarcoma effect, we established a xenograft model of zebrafish and employed U2OS cells for in vivo and in vitro assays. The animal data showed that TB significantly inhibited the tumour growth with stronger effect than that of chemotherapy. The cellular data confirmed that TB-triggered DNA damage and induced apoptosis of U2OS cells by regulation of Mki67, PARP, caspase 3 and H2AX, and Western blot assay showed an activation of p53 signalling pathway. When P53 was knocked down by siRNA, the subsequent downstream signalling was blocked, indicating a p53-dependent mechanism of TB on U2OS cells (p53 wt). Using osteosarcoma cell lines with p53 mutations (HOS, SAOS-2 and MG63), we found that TB exerted stronger inhibitory effect on U2OS cells than that on p53-mut cell lines, but it also exerted obvious effect on SAOS-2 cells (p53 null), suggesting an activation of p53-independent pathway in the p53-null cells. Interestingly, theabrownin was found to have no toxicity on normal tissue in vivo and could even increase the viability of p53-wt normal cells. In sum, theabrownin could trigger DNA damage and induce apoptosis on U2OS cells via a p53-dependent mechanism, being a promising candidate for osteosarcoma therapy.

Date of acceptance

2018

Autoren

Wangdong Jin
Li Zhou
Bo Yan
Li Yan
Fucun Liu
Peijian Tong
Wenhua Yu
Xiaoqiao Dong
Li Xie
Jin Zhang
Yiqiao Xu
Chunqi Li
Qiang Yuan
Letian Shan
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/29993186

DOI

10.1111/jcmm.13742

eISSN

1582-4934

Externe Identifier

PubMed Central ID: PMC6111873

Ausgabe der Veröffentlichung

9

Zeitschrift

J Cell Mol Med

Schlüsselwörter

DNA damage
P53
osteosarcoma
theabrownin
zebrafish
Animals
Antineoplastic Agents, Phytogenic
Apoptosis
Bone Neoplasms
Caspase 3
Catechin
Cell Cycle
Cell Line, Tumor
Cell Survival
Cisplatin
DNA Damage
Gene Expression Regulation, Neoplastic
Histones
Humans
Ki-67 Antigen
Larva
Mesenchymal Stem Cells
Osteoblasts
Osteosarcoma
Poly(ADP-ribose) Polymerases
RNA, Small Interfering
Signal Transduction
Tumor Suppressor Protein p53
Xenograft Model Antitumor Assays
Zebrafish

Sprache

eng

Country

England

Paginierung

4423 - 4436

Datum der Veröffentlichung

2018

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2019

Titel

Theabrownin triggers DNA damage to suppress human osteosarcoma U2OS cells by activating p53 signalling pathway.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

22

Data source: PubMed

Theabrownin triggers DNA damage to suppress human osteosarcoma U2OS cells by activating p53 signalling pathway

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