Investigation in the selective targeting of homologous recombination-deficient cells by benzophenanthridine alkaloid nitidine.

Authors

Yoshihiro Nishida, Takeshi Terabayashi, Sawako Adachi, Tomoko Okuma, Toshimasa Ishizaki, Tadashi Tomo, Katsuhiro Hanada

Published in

Scientific reports. Jul 08, 2026. Epub Jul 08, 2026.

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.

PMID:
42420426
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

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