Evidence map›Paper›PMID 31551535›Full record

ArticleScientific reports2019

Chrysin enhances anticancer drug-induced toxicity mediated by the reduction of claudin-1 and 11 expression in a spheroid culture model of lung squamous cell carcinoma cells.

Ryohei Maruhashi, Hiroaki Eguchi, Risa Akizuki, Shohei Hamada, Takumi Furuta, Toshiyuki Matsunaga, Satoshi Endo, Kenji Ichihara, Akira Ikari

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 15% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
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  5. Chrysin induces cell death and inhibits migration and invasion in squamous cervical carcinoma using a three-dimensional cell culture model.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025
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  14. CYP1B1 as a therapeutic target in cardio-oncology.Clinical science (London, England : 1979) · 2020
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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

9 authors at 3 institutions in 1 country.

Ryohei MaruhashiLaboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu, 501-1196, Japan.
Hiroaki EguchiLaboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu, 501-1196, Japan.
Risa AkizukiLaboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu, 501-1196, Japan.
Shohei HamadaDepartment of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8414, Japan.
Takumi FurutaDepartment of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8414, Japan.
Toshiyuki MatsunagaEducation Center of Green Pharmaceutical Sciences, Gifu Pharmaceutical University, Gifu, 502-8585, Japan.
Satoshi EndoLaboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu, 501-1196, Japan.
Kenji IchiharaNagaragawa Research Center, API Co., Ltd., Gifu, 502-0071, Japan.
Akira IkariLaboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu, 501-1196, Japan. ikari@gifu-pu.ac.jp.ORCID http://orcid.org/0000-0003-2696-0897
Gifu Pharmaceutical University · JPKyoto Pharmaceutical University · JPNagara Medical Center · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The aberrant expression of claudins (CLDNs), which are tight junctional proteins, is seen in various solid tumors, but the regulatory mechanisms and their pathophysiological role are not well understood. Both CLDN1 and CLDN11 were highly expressed in human lung squamous cell carcinoma (SCC). Chrysin, found in high concentration in honey and propolis, decreased CLDN1 and CLDN11 expression in RERF-LC-AI cells derived from human lung SCC. The phosphorylation level of Akt was decreased by chrysin, but those of ERK1/2 and c-Jun were not. LY-294002, an inhibitor of phosphatidylinositol 3-kinase, inhibited the phosphorylation of Akt and decreased the expression levels of CLDN1 and CLDN11. The association between phosphoinositide-dependent kinase 1 (PDK1) and Akt was inhibited by chrysin, but the phosphorylation of PDK1 was not. Immunoprecipitation and quartz-crystal microbalance assays revealed that biotinylated-chrysin binds directly to Akt. The knockdown of CLDN1 and CLDN11 using small interfering RNAs increased the transepithelial flux of doxorubicin (DXR), an anthracycline anticancer drug. Similarly, both chrysin and LY-294002 increased DXR flux. Neither CLDN1 knockdown, CLDN11 knockdown, nor chrysin changed the anticancer drug-induced cytotoxicity in a two-dimensional culture model, whereas they enhanced cytotoxicity in a spheroid culture model. Taken together, chrysin may bind to Akt and inhibit its phosphorylation, resulting in the elevation of anticancer drug-induced toxicity mediated by reductions in CLDN1 and CLDN11 expression in RERF-LC-AI cells. We suggest that chrysin may be useful as an adjuvant chemotherapy in lung SCC.

Indexed as

Adenocarcinoma of LungAntineoplastic AgentsCarcinoma, Squamous CellCell Line, TumorClaudin-1ClaudinsDoxorubicinFlavonoidsGene Expression Regulation, NeoplasticHumansLung NeoplasmsPhosphorylationAntineoplastic AgentschrysinClaudin-1ClaudinsCLDN11 protein, humanCLDN1 protein, humanDoxorubicinFlavonoids

Identifiers

PMID31551535
PMCPMC6760125
OpenAlexW2975784527

What OpenQuestion holds

Textmetadata
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.