Evidence map›Paper›PMID 26991801›Full record

ArticleChemical research in toxicology2016

Epigenetics Reactivation of Nrf2 in Prostate TRAMP C1 Cells by Curcumin Analogue FN1.

Wenji Li, Doug Pung, Zheng-Yuan Su, Yue Guo, Chengyue Zhang, Anne Yuqing Yang, Xi Zheng, Zhi-Yun Du, Kun Zhang, Ah-Ng Kong

Abstract read
In one paragraph

Article in Chemical research in toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 7% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.

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  12. Epigenetics of Muscle- and Brain-Specific Expression of KLHL Family Genes.International journal of molecular sciences · 2020
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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 3 countries.

Wenji LiCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.
Doug PungCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.
Zheng-Yuan SuCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.
Yue GuoCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.
Chengyue ZhangCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.
Anne Yuqing YangCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.
Xi ZhengSusan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , 164 Frelinghuysen Road, Piscataway, New Jersey 08854, United States.
Zhi-Yun DuAllan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology , Guangzhou, P.R. China.
Kun ZhangLaboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology , Guangzhou, China.
Ah-Ng KongCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.
Rutgers, The State University of New Jersey · USGuangdong University of Technology · CNChung Yuan Christian University · TW

Funding

Curcuma Longa: epigenetic effects in prostate and colon cancerR01AT007065 · NCCIH · RUTGERS, THE STATE UNIV OF N.J. · PI KONG, AH-NG TONY · 2012 to 2016
$2.3M
NCCIH NIH HHS R01 AT007065NCCIH NIH HHS R01AT007065
6 · The paper itself

Abstract

It has previously been shown that curcumin can effectively inhibit prostate cancer proliferation and progression in TRAMP mice, potentially acting through the hypomethylation of the Nrf2 gene promoter and hence activation of the Nrf2 pathway to enhance cell antioxidative defense. FN1 is a synthetic curcumin analogue that shows stronger anticancer activity than curcumin in other reports. We aimed to explore the epigenetic modification of FN1 that restores Nrf2 expression in TRAMP-C1 cells. Stably transfected HepG2-C8 cells were used to investigate the effect of FN1 on the Nrf2- antioxidant response element (ARE) pathway. Real-time quantitative PCR and Western blotting were applied to study the influence of FN1 on endogenous Nrf2 and its downstream genes. Bisulfite genomic sequencing (BGS) and methylated DNA immunoprecipitation (MeDIP) were then performed to examine the methylation profile of the Nrf2 promoter. An anchorage-independent colony-formation analysis was conducted to examine the tumor inhibition activity of FN1. Epigenetic modification enzymes, including DNMTs and HDACs, were investigated by Western blotting. The luciferase reporter assay indicated that FN1 was more potent than curcumin in activating the Nrf2-ARE pathway. FN1 increased the expression of Nrf2 and its downstream detoxifying enzymes. FN1 significantly inhibited the colony formation of TRAMP-C1 cells. BGS and MeDIP assays revealed that FN1 treatment (250 nM for 3 days) reduced the percentage of CpG methylation of the Nrf2 promoter. FN1 also downregulated epigenetic modification enzymes. In conclusion, our results suggest that FN1 is a novel anticancer agent for prostate cancer. In the TRAMP-C1 cell line, FN1 can increase the level of Nrf2 and downstream genes via activating the Nrf2-ARE pathway and inhibit the colony formation potentially through the decreased expression of keap1 coupled with CpG demethylation of the Nrf2 promoter. This CpG demethylation effect may come from decreased epigenetic modification enzymes, such as DNMT1, DNMT3a, DNMT3b, and HDAC4.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorCpG IslandsCurcuminDNA MethylationEpigenesis, GeneticGene Expression Regulation, NeoplasticHumansKelch-Like ECH-Associated Protein 1MaleMiceNF-E2-Related Factor 2ProstateProstatic NeoplasmsAntineoplastic AgentsCurcuminKelch-Like ECH-Associated Protein 1Nfe2l2 protein, mouseNF-E2-Related Factor 2

Identifiers

PMID26991801
PMCPMC4955590
OpenAlexW2323737924

What OpenQuestion holds

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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.