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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月8日

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

摘要

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.