Evidence map›Paper›PMID 22927901›Full record

ArticlePloS one2012

Clitocine reversal of P-glycoprotein associated multi-drug resistance through down-regulation of transcription factor NF-κB in R-HepG2 cell line.

Jianguo Sun, Chilam Au Yeung, Ngai Na Co, Tsun Yee Tsang, Esmond Yau, Kewang Luo, Ping Wu, Judy Chan Yuet Wa, Kwok-Pui Fung, Tim-Tak Kwok and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

20 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. The Small Molecules of Plant Origin with Anti-Glioma Activity.International journal of molecular sciences · 2025
    Review
  3. Article
  4. Natural Inhibitors of P-glycoprotein in Acute Myeloid Leukemia.International journal of molecular sciences · 2023
    Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. [Role of inhibition of nuclear factor-kappa B gene transcription by specific miRNA in reversing multi-drug resistance of liver cancer].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2016
    Article
  16. Article
  17. Article
  18. Article
  19. Silencing clusterin gene transcription on effects of multidrug resistance reversing of human hepatoma HepG2/ADM cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
    Article
  20. Article
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

11 authors at 2 institutions in 1 country.

Jianguo SunZhejiang University, Research Centre of Siyuan Natural Pharmacy and Biotoxicology, College of Life Sciences, Zijinggang Campus, Hangzhou, People's Republic of China.
Chilam Au Yeung
Ngai Na Co
Tsun Yee Tsang
Esmond Yau
Kewang Luo
Ping Wu
Judy Chan Yuet Wa
Kwok-Pui Fung
Tim-Tak Kwok
Feiyan Liu
Chinese University of Hong Kong · CNZhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multidrug resistance (MDR) is one of the major reasons for failure in cancer chemotherapy and its suppression may increase the efficacy of therapy. The human multidrug resistance 1 (MDR1) gene encodes the plasma membrane P-glycoprotein (P-gp) that pumps various anti-cancer agents out of the cancer cell. R-HepG2 and MES-SA/Dx5 cells are doxorubicin induced P-gp over-expressed MDR sublines of human hepatocellular carcinoma HepG2 cells and human uterine carcinoma MES-SA cells respectively. Herein, we observed that clitocine, a natural compound extracted from Leucopaxillus giganteus, presented similar cytotoxicity in multidrug resistant cell lines compared with their parental cell lines and significantly suppressed the expression of P-gp in R-HepG2 and MES-SA/Dx5 cells. Further study showed that the clitocine increased the sensitivity and intracellular accumulation of doxorubicin in R-HepG2 cells accompanying down-regulated MDR1 mRNA level and promoter activity, indicating the reversal effect of MDR by clitocine. A 5'-serial truncation analysis of the MDR1 promoter defined a region from position -450 to -193 to be critical for clitocine suppression of MDR1. Mutation of a consensus NF-κB binding site in the defined region and overexpression of NF-κB p65 could offset the suppression effect of clitocine on MDR1 promoter. By immunohistochemistry, clitocine was confirmed to suppress the protein levels of both P-gp and NF-κB p65 in R-HepG2 cells and tumors. Clitocine also inhibited the expression of NF-κB p65 in MES-SA/Dx5. More importantly, clitocine could suppress the NF-κB activation even in presence of doxorubicin. Taken together; our results suggested that clitocine could reverse P-gp associated MDR via down-regulation of NF-κB.

Indexed as

Antineoplastic AgentsATP Binding Cassette Transporter, Subfamily B, Member 1Cell ProliferationDown-RegulationDrug Resistance, MultipleGene Expression Regulation, NeoplasticHep G2 CellsHumansPromoter Regions, GeneticPyrimidine NucleosidesTranscription Factor RelAX-Linked Inhibitor of Apoptosis ProteinAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily B, Member 1clitocinePyrimidine NucleosidesTranscription Factor RelAX-Linked Inhibitor of Apoptosis Protein

Identifiers

PMID22927901
PMCPMC3425549
OpenAlexW2165721913

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.