Identification and preclinical evaluation of the small molecule, NSC745887, for treating glioblastomas via suppressing DcR3- associated signaling pathways

Li Yun Fann, Ying Chen, Da Chen Chu, Shao Ju Weng, Heng Cheng Chu, Alexander T.H. Wu, Jiann Fong Lee, Ahmed Atef Ahmed Ali, Tsung Chih Chen, Hsu Shan Huang, Kuo Hsing Ma

研究成果: 雜誌貢獻文章

2 引文 (Scopus)

摘要

The small-molecule naphtha [2,3-f]quinoxaline-7,12-dione (NSC745887) can effectively inhibit the proliferation of various cancers by trapping DNA-topoisomerase cleavage. The aim of this study was to elucidate cellular responses of NSC745887 in human glioblastoma multiforme (GBM, U118MG and U87MG cells) and investigate the underlying molecular mechanisms. NSC745887 reduced the cell survival rate and increased the sub-G1 population in dose- and time-dependent manners in GBM cells. Moreover, NSC745887 increased expression of γH2AX and caused DNA fragmentation leading to DNA damage. Furthermore, Annexin V/propidium iodide and Br-dTP staining showed the apoptotic effect of NSC745887 in GBM cells. DNA repair proteins of ataxia-telangiectasia mutated (ATM), ATM and Rad3-related, and decoy receptor 3 also decreased with NSC745887 treatment. In addition, NSC745887 caused apoptosis by the caspase-8/9-caspase-3-poly(ADP-ribose) polymerase cascade. An in vivo study indicated that NSC745887 suppressed the [18F]-FDG-specific uptake value in brain tumors. Histological staining also indicated a decrease in Ki-67 and increases in γH2AX and cleaved caspase-3 in the brain tumor area. These data provide preclinical evidence for NSC745887 as a potential new small molecule drug for managing glioblastomas.
原文英語
頁(從 - 到)11922-11937
頁數16
期刊Oncotarget
9
發行號15
DOIs
出版狀態已發佈 - 一月 1 2018

指紋

Glioblastoma
Brain Neoplasms
Caspase 3
Ataxia Telangiectasia Mutated Proteins
Staining and Labeling
Ataxia Telangiectasia
Quinoxalines
Type I DNA Topoisomerase
Poly(ADP-ribose) Polymerases
Caspase 9
Caspase 8
Propidium
Annexin A5
Fluorodeoxyglucose F18
DNA Fragmentation
DNA Repair
DNA Damage
Cell Survival
Apoptosis
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Oncology

引用此文

Identification and preclinical evaluation of the small molecule, NSC745887, for treating glioblastomas via suppressing DcR3- associated signaling pathways. / Fann, Li Yun; Chen, Ying; Chu, Da Chen; Weng, Shao Ju; Chu, Heng Cheng; Wu, Alexander T.H.; Lee, Jiann Fong; Ali, Ahmed Atef Ahmed; Chen, Tsung Chih; Huang, Hsu Shan; Ma, Kuo Hsing.

於: Oncotarget, 卷 9, 編號 15, 01.01.2018, p. 11922-11937.

研究成果: 雜誌貢獻文章

Fann, Li Yun ; Chen, Ying ; Chu, Da Chen ; Weng, Shao Ju ; Chu, Heng Cheng ; Wu, Alexander T.H. ; Lee, Jiann Fong ; Ali, Ahmed Atef Ahmed ; Chen, Tsung Chih ; Huang, Hsu Shan ; Ma, Kuo Hsing. / Identification and preclinical evaluation of the small molecule, NSC745887, for treating glioblastomas via suppressing DcR3- associated signaling pathways. 於: Oncotarget. 2018 ; 卷 9, 編號 15. 頁 11922-11937.
@article{199ff2f57dcf49f89557c4a9e165f4f3,
title = "Identification and preclinical evaluation of the small molecule, NSC745887, for treating glioblastomas via suppressing DcR3- associated signaling pathways",
abstract = "The small-molecule naphtha [2,3-f]quinoxaline-7,12-dione (NSC745887) can effectively inhibit the proliferation of various cancers by trapping DNA-topoisomerase cleavage. The aim of this study was to elucidate cellular responses of NSC745887 in human glioblastoma multiforme (GBM, U118MG and U87MG cells) and investigate the underlying molecular mechanisms. NSC745887 reduced the cell survival rate and increased the sub-G1 population in dose- and time-dependent manners in GBM cells. Moreover, NSC745887 increased expression of γH2AX and caused DNA fragmentation leading to DNA damage. Furthermore, Annexin V/propidium iodide and Br-dTP staining showed the apoptotic effect of NSC745887 in GBM cells. DNA repair proteins of ataxia-telangiectasia mutated (ATM), ATM and Rad3-related, and decoy receptor 3 also decreased with NSC745887 treatment. In addition, NSC745887 caused apoptosis by the caspase-8/9-caspase-3-poly(ADP-ribose) polymerase cascade. An in vivo study indicated that NSC745887 suppressed the [18F]-FDG-specific uptake value in brain tumors. Histological staining also indicated a decrease in Ki-67 and increases in γH2AX and cleaved caspase-3 in the brain tumor area. These data provide preclinical evidence for NSC745887 as a potential new small molecule drug for managing glioblastomas.",
keywords = "Animal-PET, Decoy receptor 3 (DcR3), Naphtho [2,3-f]quinoxaline-7,12-dione, [F]-FDG",
author = "Fann, {Li Yun} and Ying Chen and Chu, {Da Chen} and Weng, {Shao Ju} and Chu, {Heng Cheng} and Wu, {Alexander T.H.} and Lee, {Jiann Fong} and Ali, {Ahmed Atef Ahmed} and Chen, {Tsung Chih} and Huang, {Hsu Shan} and Ma, {Kuo Hsing}",
year = "2018",
month = "1",
day = "1",
doi = "10.18632/oncotarget.23714",
language = "English",
volume = "9",
pages = "11922--11937",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "15",

}

TY - JOUR

T1 - Identification and preclinical evaluation of the small molecule, NSC745887, for treating glioblastomas via suppressing DcR3- associated signaling pathways

AU - Fann, Li Yun

AU - Chen, Ying

AU - Chu, Da Chen

AU - Weng, Shao Ju

AU - Chu, Heng Cheng

AU - Wu, Alexander T.H.

AU - Lee, Jiann Fong

AU - Ali, Ahmed Atef Ahmed

AU - Chen, Tsung Chih

AU - Huang, Hsu Shan

AU - Ma, Kuo Hsing

PY - 2018/1/1

Y1 - 2018/1/1

N2 - The small-molecule naphtha [2,3-f]quinoxaline-7,12-dione (NSC745887) can effectively inhibit the proliferation of various cancers by trapping DNA-topoisomerase cleavage. The aim of this study was to elucidate cellular responses of NSC745887 in human glioblastoma multiforme (GBM, U118MG and U87MG cells) and investigate the underlying molecular mechanisms. NSC745887 reduced the cell survival rate and increased the sub-G1 population in dose- and time-dependent manners in GBM cells. Moreover, NSC745887 increased expression of γH2AX and caused DNA fragmentation leading to DNA damage. Furthermore, Annexin V/propidium iodide and Br-dTP staining showed the apoptotic effect of NSC745887 in GBM cells. DNA repair proteins of ataxia-telangiectasia mutated (ATM), ATM and Rad3-related, and decoy receptor 3 also decreased with NSC745887 treatment. In addition, NSC745887 caused apoptosis by the caspase-8/9-caspase-3-poly(ADP-ribose) polymerase cascade. An in vivo study indicated that NSC745887 suppressed the [18F]-FDG-specific uptake value in brain tumors. Histological staining also indicated a decrease in Ki-67 and increases in γH2AX and cleaved caspase-3 in the brain tumor area. These data provide preclinical evidence for NSC745887 as a potential new small molecule drug for managing glioblastomas.

AB - The small-molecule naphtha [2,3-f]quinoxaline-7,12-dione (NSC745887) can effectively inhibit the proliferation of various cancers by trapping DNA-topoisomerase cleavage. The aim of this study was to elucidate cellular responses of NSC745887 in human glioblastoma multiforme (GBM, U118MG and U87MG cells) and investigate the underlying molecular mechanisms. NSC745887 reduced the cell survival rate and increased the sub-G1 population in dose- and time-dependent manners in GBM cells. Moreover, NSC745887 increased expression of γH2AX and caused DNA fragmentation leading to DNA damage. Furthermore, Annexin V/propidium iodide and Br-dTP staining showed the apoptotic effect of NSC745887 in GBM cells. DNA repair proteins of ataxia-telangiectasia mutated (ATM), ATM and Rad3-related, and decoy receptor 3 also decreased with NSC745887 treatment. In addition, NSC745887 caused apoptosis by the caspase-8/9-caspase-3-poly(ADP-ribose) polymerase cascade. An in vivo study indicated that NSC745887 suppressed the [18F]-FDG-specific uptake value in brain tumors. Histological staining also indicated a decrease in Ki-67 and increases in γH2AX and cleaved caspase-3 in the brain tumor area. These data provide preclinical evidence for NSC745887 as a potential new small molecule drug for managing glioblastomas.

KW - Animal-PET

KW - Decoy receptor 3 (DcR3)

KW - Naphtho [2,3-f]quinoxaline-7,12-dione

KW - [F]-FDG

UR - http://www.scopus.com/inward/record.url?scp=85042445440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042445440&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.23714

DO - 10.18632/oncotarget.23714

M3 - Article

AN - SCOPUS:85042445440

VL - 9

SP - 11922

EP - 11937

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 15

ER -