Evidence map›Paper›PMID 31994822›Full record

ArticleCancer science2020

Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway.

Keitaro Iida, Taku Naiki, Aya Naiki-Ito, Shugo Suzuki, Hiroyuki Kato, Satoshi Nozaki, Takashi Nagai, Toshiki Etani, Yuko Nagayasu, Ryosuke Ando and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
10.6field-weighted citation impact, top 1% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.

  1. Pooled it
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  6. Article
  7. The Role of Natural Compounds in Bladder Urothelial Carcinoma Treatment.International journal of molecular sciences · 2026
    Review
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  16. Article
  17. Potential anticancer effects and toxicity of flavones luteolin and apigeninJournal of environmental science and health. Part C, Toxicology and carcinogenesis · 2025
    Review
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  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

13 authors at 1 institution in 1 country.

Keitaro IidaDepartment of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Taku NaikiDepartment of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.ORCID https://orcid.org/0000-0002-7638-6048
Aya Naiki-ItoDepartment of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.ORCID https://orcid.org/0000-0003-0828-2033
Shugo SuzukiDepartment of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.ORCID https://orcid.org/0000-0001-8938-9670
Hiroyuki KatoDepartment of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Satoshi NozakiDepartment of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Takashi NagaiDepartment of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Toshiki EtaniDepartment of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Yuko NagayasuDepartment of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Ryosuke AndoDepartment of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Noriyasu KawaiDepartment of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Takahiro YasuiDepartment of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.ORCID https://orcid.org/0000-0003-2197-2477
Satoru TakahashiDepartment of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.ORCID https://orcid.org/0000-0002-8139-8158
Nagoya City University · JP

Funding

Aichi Health Promotion Fundation 30127Ministry of Health, Labour and Welfare 18K16705TOBE MAKI Scholarship Foundation 18-JA-501
6 · The paper itself

Abstract

Luteolin is a natural flavonoid with strong anti-oxidative properties that is reported to have an anti-cancer effect in several malignancies other than bladder cancer. In this study, we describe the effect of luteolin on a human bladder cancer cell line, T24, in the context of the regulation of p21, thioredoxin-1 (TRX1) and the mechanistic target of rapamycin (mTOR) pathway. Luteolin inhibited cell survival and induced G2/M cell-cycle arrest, p21 upregulation and downregulation of phospho(p)-S6, which is downstream of mTOR signaling. Luteolin also upregulated TRX1 and reduced intracellular reactive oxygen species production. In a subcutaneous xenograft mouse model using the rat bladder cancer cell line, BC31, tumor volumes were significantly decreased in mice orally administered luteolin compared to control. Immunohistochemical analysis revealed that increased p21 and decreased p-S6 expression were induced in the luteolin treatment group. Moreover, in another in vivo N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder cancer model, the oral administration of luteolin led to a trend of decreased bladder tumor dimension and significantly decreased the Ki67-labeling index and p-S6 expression. Furthermore, the major findings on the metabolism of luteolin suggest that both plasma and urine luteolin-3'-O-glucuronide concentrations are strongly associated with the inhibition of cell proliferation and mTOR signaling. Moreover, a significant decrease in the squamous differentiation of bladder cancer is attributed to plasma luteolin-3'-glucuronide concentration. In conclusion, luteolin, and in particular its metabolized product, may represent another natural product-derived therapeutic agent that acts against bladder cancer by upregulating p21 and inhibiting mTOR signaling.

Indexed as

AnimalsApoptosisButylhydroxybutylnitrosamineCell Line, TumorCell ProliferationDisease Models, AnimalGene Expression Regulation, NeoplasticHumansKi-67 AntigenLuteolinMaleMiceProto-Oncogene Proteins c-aktRatsrho GTP-Binding ProteinsSignal TransductionButylhydroxybutylnitrosamineKi-67 AntigenLuteolinMKI67 protein, humanmTOR protein, ratProto-Oncogene Proteins c-aktrho GTP-Binding ProteinsThioredoxinsTOR Serine-Threonine KinasesTxn1 protein, ratTXN protein, humananimal modelbladder cancerchemopreventionmTORoxidative stress

Identifiers

PMID31994822
PMCPMC7156788
OpenAlexW3003597907

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

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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.