Evidence map›Paper›PMID 39009033›Full record

ArticleCancer science2024

Cytochrome P450 2J2 is required for the natural compound austocystin D to elicit cancer cell toxicity.

Yukiko Kojima, Saki Fujieda, Liya Zhou, Masahiro Takikawa, Kouji Kuramochi, Toshiki Furuya, Ayaka Mizumoto, Noritaka Kagaya, Teppei Kawahara, Kazuo Shin-Ya and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

14 authors.

Yukiko KojimaDepartment of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.
Saki FujiedaDepartment of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.
Liya ZhouDepartment of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.
Masahiro TakikawaDepartment of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.
Kouji KuramochiDepartment of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.
Toshiki FuruyaDepartment of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.
Ayaka MizumotoDepartment of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Noritaka KagayaNational Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan.
Teppei KawaharaJapan Biological Informatics Consortium (JBIC), Tokyo, Japan.
Kazuo Shin-YaNational Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan.
Shingo DanCancer Chemotherapy Center, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan.ORCID https://orcid.org/0000-0002-0022-2725
Akihiro TomidaCancer Chemotherapy Center, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan.
Fuyuki IshikawaDepartment of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0002-5580-2305
Mahito SadaieDepartment of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.ORCID https://orcid.org/0000-0002-3443-5980

Funding

AMED JP20cm0106113JSPS KAKENHI JP20K07037MEXT KAKENHI JP19H05655
6 · The paper itself

Abstract

Austocystin D is a natural compound that induces cytochrome P450 (CYP) monooxygenase-dependent DNA damage and growth inhibition in certain cancer cell lines. Cancer cells exhibiting higher sensitivity to austocystin D often display elevated CYP2J2 expression. However, the essentiality and the role of CYP2J2 for the cytotoxicity of this compound remain unclear. In this study, we demonstrate that CYP2J2 depletion alleviates austocystin D sensitivity and DNA damage induction, while CYP2J2 overexpression enhances them. Moreover, the investigation into genes involved in austocystin D cytotoxicity identified POR and PGRMC1, positive regulators for CYP activity, and KAT7, a histone acetyltransferase. Through genetic manipulation and analysis of multiomics data, we elucidated a role for KAT7 in CYP2J2 transcriptional regulation. These findings strongly suggest that CYP2J2 is crucial for austocystin D metabolism and its subsequent cytotoxic effects. The potential use of austocystin D as a therapeutic prodrug is underscored, particularly in cancers where elevated CYP2J2 expression serves as a biomarker.

Indexed as

Cytochrome P-450 CYP2J2Cytochrome P-450 Enzyme SystemDNA DamageCell Line, TumorGene Expression Regulation, NeoplasticHumansMembrane ProteinsNeoplasmsCYP2J2 protein, humanCytochrome P-450 CYP2J2Cytochrome P-450 Enzyme SystemMembrane Proteinsaustocystin DcytotoxicityDNA damagegene expressionknockout screening

Identifiers

PMID39009033
PMCPMC11462933

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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.