Evidence map›Paper›PMID 40632344›Full record

ArticleDiscover oncology2025

Epigenetic agents, zebularine and valproic acid, inhibit the growth of the oral squamous cell carcinoma cell line HSC4 in vitro and in vivo.

Shuhei Takahashi, Koki Yoshida, Durga Paudel, Tetsuro Morikawa, Osamu Uehara, Fumiya Harada, Dedy Ariwansa, Sarita Giri, Jun Sato, Hiroki Nagayasu and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Review
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.

Shuhei TakahashiDivision of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
Koki YoshidaDivision of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
Durga PaudelAdvanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
Tetsuro MorikawaDivision of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
Osamu UeharaDivision of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
Fumiya HaradaDivision of Oral and Maxillofacial Surgery, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
Dedy AriwansaDivision of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
Sarita GiriAdvanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
Jun SatoDivision of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
Hiroki NagayasuDivision of Oral and Maxillofacial Surgery, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
Yoshihiro AbikoDivision of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan. yoshi-ab@hoku-iryo-u.ac.jp.

Funding

Japan Society for the Promotion of Science 21K10121
6 · The paper itself

Abstract

objectivesThis study explored the potential of Zebularine (Zeb), a DNA methyltransferase inhibitor (DNMTi), and Valproic acid (Vpa), a histone deacetylase inhibitor (HDACi), as a combined treatment strategy for OSCC. MATERIALS AND

methodsOSCC cell lines, HSC4 (well-differentiated type) and SAS (poorly differentiated type), were cultured and treated with Zeb, Vpa, and their combinations. Cell viability, mRNA expression of P16, P21, NPY, and RASSF1 using quantitative reverse transcription polymerase chain reaction (qRT-PCR), DNA methylation using methylation-specific PCR (qMSP), and in situ HDAC activity were analyzed in vitro. In vivo, a xenograft tumor formation assay was conducted using male BALB/Slc-nu nude mice, in accordance with the Basel Declaration and The ARRIVE guidelines 2.0. Tumor samples were analyzed by qRT-PCR, and qMSP.

resultsIn vitro experiments using the HSC4 and SAS cell lines revealed significant cytotoxic effects and upregulation of tumor suppressor genes (P16, P21, NPY, and RASSF1) after treatment with Zeb + Vpa. In vivo xenograft assay in nude mice treated with Zeb + Vpa demonstrated reduced tumor volume in HSC4 cell-transplanted tumors without significant adverse effects on the body weights of the mice, whereas no significant reduction in tumor size was observed in SAS cell-transplanted tumors compared with controls. Molecular analysis confirmed elevated gene expression levels and reduced DNA methylation percentages in the treated tumors, with a more pronounced effect in HSC4 compared to SAS.

conclusionsThese findings suggest that the combination of Zeb and Vpa holds promise as an effective and low-toxicity therapeutic strategy for well-differentiated type of OSCC.

Indexed as

EpigeneticsOral squamous cell carcinomaValproic acidZebularine

Identifiers

PMID40632344
PMCPMC12241533

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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.