Evidence map›Paper›PMID 26366213›Full record

ArticleJournal of Cancer2015

The Histone Deacetylase Inhibitor Vaproic Acid Induces Cell Growth Arrest in Hepatocellular Carcinoma Cells via Suppressing Notch Signaling.

Guangchun Sun, Lily V Mackey, David H Coy, Cui-Yun Yu, Lichun Sun

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.3field-weighted citation impact, top 11% 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, 41 citations in OpenAlex.

  1. Review
  2. Current research of the Notch pathway in hepatocellular carcinoma.European journal of medical research · 2025
    Review
  3. Short-chain fatty acids in cancer pathogenesis.Cancer metastasis reviews · 2023
    Review
  4. Article
  5. Review
  6. Abnormal activation of notch 1 signaling causes apoptosis resistance in cervical cancer.International journal of clinical and experimental pathology · 2022
    Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
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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

5 authors at 2 institutions in 1 country.

Guangchun Sun1. Department of Pharmacy, The Fifth People's Hospital of Shanghai, Fudan University; 801 He-Qing Rd., Shanghai 200240, China.
Lily V Mackey3. Department of Medicine, School of Medicine, Tulane Health Sciences Center, New Orleans, LA 70112-2699, USA.
David H Coy3. Department of Medicine, School of Medicine, Tulane Health Sciences Center, New Orleans, LA 70112-2699, USA.
Cui-Yun Yu2. Institute of Pharmacy & Pharmacology, Department of Pharmacy, University of South China, Hengyang 421001, China ; 3. Department of Medicine, School of Medicine, Tulane Health Sciences Center, New Orleans, LA 70112-2699, USA.
Lichun Sun1. Department of Pharmacy, The Fifth People's Hospital of Shanghai, Fudan University; 801 He-Qing Rd., Shanghai 200240, China ; 2. Institute of Pharmacy & Pharmacology, Department of Pharmacy, University of South China, Hengyang 421001, China ; 3. Department of Medicine, School of Medicine, Tulane Health Sciences Center, New Orleans, LA 70112-2699, USA.
Fudan University · CNUniversity of South China · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is a type of malignant cancer. Notch signaling is aberrantly expressed in HCC tissues with more evidence showing that this signaling plays a critical role in HCCs. In the present study, we investigate the effects of the anti-convulsant drug valproic acid (VPA) in HCC cells and its involvement in modulating Notch signaling. We found that VPA, acting as a histone deacetylase (HDAC) inhibitor, induced a decrease in HDAC4 and an increase in acetylated histone 4 (AcH4) and suppressed HCC cell growth. VPA also induced down-regulation of Notch signaling via suppressing the expression of Notch1 and its target gene HES1, with an increase of tumor suppressor p21 and p63. Furthermore, Notch1 activation via overexpressing Notch1 active form ICN1 induced HCC cell proliferation and anti-apoptosis, indicating Notch signaling played an oncogenic role in HCC cells. Meanwhile, VPA could reverse Notch1-induced increase of cell proliferation. Interestingly, VPA was also observed to stimulate the expression of G protein-coupled somatostatin receptor type 2 (SSTR2) that has been used in receptor-targeting therapies. This discovery supports a combination therapy of VPA with the SSTR2-targeting agents. Our in vitro assay did show that the combination of VPA and the peptide-drug conjugate camptothecin-somatostatin (CPT-SST) displayed more potent anti-proliferative effects on HCC cells than did each alone. VPA may be a potential drug candidate in the development of anti-HCC drugs via targeting Notch signaling, especially in combination with receptor-targeting cytotoxic agents.

Indexed as

HDAC inhibitorhepatocellular carcinomaNotch signalingreceptor-targeting.valproic acid

Identifiers

PMID26366213
PMCPMC4565849
OpenAlexW2409867495

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.