Evidence map›Paper›PMID 39852970›Full record

ArticleToxins2025

The Role of Indoxyl Sulfate in Exacerbating Colorectal Cancer During Chronic Kidney Disease Progression: Insights into the Akt/β-Catenin/c-Myc and AhR/c-Myc Pathways in HCT-116 Colorectal Cancer Cells.

Yu Ichisaka, Chihiro Takei, Kazuma Naito, Manami Higa, Shozo Yano, Toshimitsu Niwa, Hidehisa Shimizu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Toxins, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Fujita medical journal · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. A guide to uraemic toxicity.Nature reviews. Nephrology · 2026
    Review
  10. Review
  11. Review
  12. 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

7 authors.

Yu IchisakaGraduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-cho, Matsue 690-8504, Shimane, Japan.
Chihiro TakeiGraduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-cho, Matsue 690-8504, Shimane, Japan.
Kazuma NaitoGraduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-cho, Matsue 690-8504, Shimane, Japan.
Manami HigaGraduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-cho, Matsue 690-8504, Shimane, Japan.
Shozo YanoFaculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Shimane, Japan.ORCID 0000-0002-9210-2949
Toshimitsu NiwaShubun University, 6 Nikko-cho, Ichinomiya 491-0938, Aichi, Japan.
Hidehisa ShimizuGraduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-cho, Matsue 690-8504, Shimane, Japan.ORCID 0000-0002-0939-0098

Funding

Ministry of Education, Culture, Sports, Science and Technology JP21H03356
6 · The paper itself

Abstract

Epidemiological studies suggest an increased risk of colorectal cancer (CRC) aggravation in patients with chronic kidney disease (CKD). Our previous study demonstrated that indoxyl sulfate, a uremic toxin whose concentration increases with CKD progression, exacerbates CRC through activation of the AhR and Akt pathways. Consequently, indoxyl sulfate has been proposed to be a significant link between CKD progression and CRC aggravation. The present study aimed to investigate the roles of c-Myc and β-Catenin, which are hypothesized to be downstream factors of indoxyl sulfate-induced AhR and Akt activation, in CRC cell proliferation and EGF sensitivity in HCT-116 CRC cells. Indoxyl sulfate significantly induced CRC cell proliferation at concentrations exceeding 62.5 µM, a process suppressed by the c-Myc inhibitor 10058-F4. Indoxyl sulfate activated the Akt/β-Catenin/c-Myc pathway as evidenced by the Akt inhibitor MK2206, which decreased both β-Catenin and c-Myc protein levels, and the β-Catenin inhibitor XAV-939, which reduced c-Myc protein levels. The AhR antagonist CH223191 also inhibited c-Myc upregulation, indicating involvement of the AhR/c-Myc pathway. MK2206 partially attenuated the indoxyl sulfate-induced AhR transcriptional activity, suggesting that Akt activation influences the AhR/c-Myc pathway. MK2206, CH223191, and 10058-F4 suppressed the increase in EGFR protein levels induced by indoxyl sulfate, indicating that the Akt/β-Catenin/c-Myc and AhR/c-Myc pathways enhance the sensitivity of HCT-116 CRC cells to EGF. These findings indicate that the elevation of indoxyl sulfate levels in the blood, due to CKD progression, could worsen CRC by promoting the proliferation of CRC cells and enhancing EGF signaling. Therefore, indoxyl sulfate could potentially serve as a therapeutic target for CRC aggravation in patients with CKD.

Indexed as

Colorectal NeoplasmsIndicanProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mycRenal Insufficiency, ChronicBasic Helix-Loop-Helix Proteinsbeta CateninCell ProliferationDisease ProgressionHCT116 CellsHumansReceptors, Aryl HydrocarbonSignal TransductionAHR protein, humanBasic Helix-Loop-Helix Proteinsbeta CateninCTNNB1 protein, humanIndicanMYC protein, humanProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mycReceptors, Aryl HydrocarbonAhRAktchronic kidney diseasec-Myccolorectal cancerEGFRgut microbiotaindole derivativeIndoxyl sulfatetryptophan metabolitesβ-Catenin

Identifiers

PMID39852970
PMCPMC11769072

What OpenQuestion holds

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LicenceCC BY
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.