Evidence map›Paper›PMID 39657606›Full record

ArticlePathobiology : journal of immunopathology, molecular and cellular biology2025

Metabolic Analysis of Three-Dimensional Cultured Gastrointestinal Cancer Cells Suggests that <sc>l</sc>-Arginine Inhibits Tumor Growth by Affecting the Urea Cycle.

Eri Tanaka, Naoko Taniura, Ken-Ichi Mukaisho, Yusuke Kageyama, Mai Noujima, Hirohito Ishigaki, Takahisa Nakayama, Ryoji Kushima

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pathobiology : journal of immunopathology, molecular and cellular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Eri TanakaDivision of Human Pathology, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
Naoko TaniuraEducation Center for Medicine and Nursing, Shiga University of Medical Science, Otsu, Japan.
Ken-Ichi MukaishoEducation Center for Medicine and Nursing, Shiga University of Medical Science, Otsu, Japan.
Yusuke KageyamaDivision of Human Pathology, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
Mai NoujimaDivision of Human Pathology, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
Hirohito IshigakiDivision of Pathogenesis and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
Takahisa NakayamaDivision of Human Pathology, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
Ryoji KushimaDivision of Human Pathology, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThere is evidence for the anticancer effects of <sc>l</sc>-arginine (arginine); however, the direct effects on cancer cells and mechanism of action are unclear.

methodsVarious upper gastrointestinal cancer cells (OE19, OE33, MKN1, MKN45, MKN74, and AGS) were divided into arginine-treated and -untreated groups and cultured using two-dimensional and three-dimensional culture systems. Proliferation was evaluated using the MTT assay to identify arginine-sensitive (OE33) and arginine-insensitive (OE19) strains. Furthermore, the effects of arginine were evaluated using a mitochondrial stress test, cell cycle assay, comprehensive metabolic analysis, and tracer study using (13C6) <sc>l</sc>-arginine.

resultsIn OE33 (but not in OE19), the maximal respiratory capacity of mitochondria was lower in the treated group than in the control group. In OE33, S phase cells (determined using BrdU) were significantly reduced. In a comprehensive metabolic analysis of OE33, citrulline/ornithine levels were significantly lower in arginine-treated than in untreated cells. Using OE33, carbamoyl aspartic acid (CAA) levels were significantly lower in arginine-treated than in untreated cells. A tracer study suggested that arginine promotes the urea cycle.

conclusionArginine affected urea cycle metabolism, thereby decreasing CAA, which is required for pyrimidine nucleotide synthesis. These findings provide insight into the mechanism underlying the anticancer effects of arginine.

Indexed as

ArginineGastrointestinal NeoplasmsUreaCell Culture Techniques, Three DimensionalCell CycleCell Line, TumorCell ProliferationHumansMitochondriaTumor Cells, CulturedArginineUreaAnticancer effectsArginineGastrointestinal cancerTumor metabolismUrea cycle

Identifiers

PMID39657606
PMCPMC12136530

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