| RRC ID |
89522
|
| 著者 |
Nishida Y, Terabayashi T, Adachi S, Okuma T, Ishizaki T, Tomo T, Hanada K.
|
| タイトル |
Investigation in the selective targeting of homologous recombination-deficient cells by benzophenanthridine alkaloid nitidine.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Homologous recombination (HR) plays a crucial role in maintaining genome integrity in mammalian cells. In this study, a natural product screening indicated that the benzophenanthridine alkaloid nitidine chloride (NC) could selectively kill HR-deficient cells. Mechanistically, this selective cytotoxicity of NC results from the induction of double-strand breaks (DSBs) at DNA replication sites because a single-ended DSB is preferentially repaired by HR. Poly ADP ribose polymerase inhibitors, such as olaparib (OLA), have been developed as HR-targeted drugs. Interestingly, NC treatment resulted in cytotoxic effects in OLA-resistant cells, with an NC/OLA combination treatment showing additive effects on cytotoxicity in HR-deficient cells. With its ability to kill HR-deficient cancer cells, NC has potential as a treatment for hereditary breast and ovary cancer syndrome.
|
| 公開日 |
2026-7-8
|
| DOI |
10.1038/s41598-026-61663-8
|
| PII |
10.1038/s41598-026-61663-8
|
| PMID |
42420426
|
| リソース情報 |
| ヒト・動物細胞 |
XR-V15B(RCB2339)
EM-9(RCB2327)
V-3(RCB2329) |
