論文 - 詳細
| RRC ID | 81124 |
|---|---|
| 著者 | Kojima Y, Fujieda S, Zhou L, Takikawa M, Kuramochi K, Furuya T, Mizumoto A, Kagaya N, Kawahara T, Shin-Ya K, Dan S, Tomida A, Ishikawa F, Sadaie M. |
| タイトル | Cytochrome P450 2J2 is required for the natural compound austocystin D to elicit cancer cell toxicity. |
| ジャーナル | Cancer Sci |
| 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. |
| 公開日 | 2024-7-15 |
| DOI | 10.1111/cas.16289 |
| PMID | 39009033 |
| PMC | PMC11462933 |
| MeSH | Cell Line, Tumor Cytochrome P-450 CYP2J2* Cytochrome P-450 Enzyme System* / genetics Cytochrome P-450 Enzyme System* / metabolism DNA Damage* / drug effects Gene Expression Regulation, Neoplastic / drug effects Humans Membrane Proteins / genetics Membrane Proteins / metabolism Neoplasms / drug therapy Neoplasms / genetics Neoplasms / metabolism Neoplasms / pathology |
| IF | 4.966 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 20 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | NOS-2(RCB1033) HuO-3N1(RCB2104) HuO 9N2 (O9N2)(RCB2532) MG-63(RCB190) NOS-1(RCB1032) |