| RRC ID |
81124
|
| Author |
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.
|
| Title |
Cytochrome P450 2J2 is required for the natural compound austocystin D to elicit cancer cell toxicity.
|
| Journal |
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.
|
| Published |
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
|
| Resource |
| Human and Animal Cells |
NOS-2(RCB1033)
HuO-3N1(RCB2104)
HuO 9N2 (O9N2)(RCB2532)
MG-63(RCB190)
NOS-1(RCB1032) |
