Evidence map›Paper›PMID 21828038›Full record

ArticleThe Journal of biological chemistry2011

Dietary isothiocyanate-induced apoptosis via thiol modification of DNA topoisomerase IIα.

Ren-Kuo Lin, Nai Zhou, Yi Lisa Lyu, Yuan-Chin Tsai, Chang-Hsien Lu, John Kerrigan, Yu-tsung Chen, Ziqiang Guan, Tao-Shih Hsieh, Leroy F Liu

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 53 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Ren-Kuo LinDepartment of Pharmacology and the Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Jersey 08854, USA.
Nai Zhou
Yi Lisa Lyu
Yuan-Chin Tsai
Chang-Hsien Lu
John Kerrigan
Yu-tsung Chen
Ziqiang Guan
Tao-Shih Hsieh
Leroy F Liu
Rutgers, The State University of New Jersey · USDuke University · USChiayi Chang Gung Memorial Hospital · TW

Funding

MECHANISMS OF ACTION IN ANTITUMOR DRUGSR01CA039662 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI LIU, LEROY F · 1985 to 2013
$3.8M
Mechanism of Action of TOP2-Directed Anticancer DrugsR01CA102463 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI LIU, LEROY F · 2004 to 2012
$2.6M
NCI NIH HHS CA102463NCI NIH HHS CA39662NCI NIH HHS R01 CA039662NCI NIH HHS R01 CA102463
6 · The paper itself

Abstract

Studies in animal models have indicated that dietary isothiocyanates (ITCs) exhibit cancer preventive activities through carcinogen detoxification-dependent and -independent mechanisms. The carcinogen detoxification-independent mechanism of cancer prevention by ITCs has been attributed at least in part to their ability to induce apoptosis of transformed (initiated) cells (e.g. through suppression of IκB kinase and nuclear factor κB as well as other proposed mechanisms). In the current studies we show that ITC-induced apoptosis of oncogene-transformed cells involves thiol modification of DNA topoisomerase II (Top2) based on the following observations. 1) siRNA-mediated knockdown of Top2α in both SV40-transformed MEFs and Ras-transformed human mammary epithelial MCF-10A cells resulted in reduced ITC sensitivity. 2) ITCs, like some anticancer drugs and cancer-preventive dietary components, were shown to induce reversible Top2α cleavage complexes in vitro. 3) ITC-induced Top2α cleavage complexes were abolished by co-incubation with excess glutathione. In addition, proteomic analysis revealed that several cysteine residues on human Top2α were covalently modified by benzyl-ITC, suggesting that ITC-induced Top2α cleavage complexes may involve cysteine modification. Interestingly, consistent with the thiol modification mechanism for Top2α cleavage complex induction, the thiol-reactive selenocysteine, but not the non-thiol-reactive selenomethionine, was shown to induce Top2α cleavage complexes. In the aggregate, our results suggest that thiol modification of Top2α may contribute to apoptosis induction in transformed cells by ITCs.

Indexed as

DietAnimalsAntigens, NeoplasmApoptosisCell Line, TransformedCell Line, TumorCell ProliferationCysteineDNA-Binding ProteinsDNA DamageDNA FragmentationDNA Topoisomerases, Type IIFibroblastsGene Knockdown TechniquesGene SilencingHistonesAntigens, Neoplasmbenzyl isothiocyanateCysteineDNA-Binding ProteinsDNA Topoisomerases, Type IIH2AX protein, humanHistonesIsothiocyanatesisothiocyanic acidNucleosomesphenethyl isothiocyanatePoly-ADP-Ribose Binding Proteinsras ProteinsRNA, Small InterferingSulfhydryl CompoundsTOP2A protein, humanTop2a protein, mouse

Identifiers

PMID21828038
PMCPMC3190902
OpenAlexW2092837160

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.