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Cu(II) complex that synergistically potentiates cytotoxicity and an antitumor immune response by targeting cellular redox homeostasis.
Huang, Ke-Bin; Wang, Feng-Yang; Lu, Yuan; Yang, Liang-Mei; Long, Nian; Wang, Shan-Shan; Xie, Zhiying; Levine, Matthew; Zou, Taotao; Sessler, Jonathan L; Liang, Hong.
Afiliación
  • Huang KB; Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
  • Wang FY; Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
  • Lu Y; Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
  • Yang LM; Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
  • Long N; Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
  • Wang SS; Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
  • Xie Z; Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Science, Sun Yat-Sen University, Guangzhou 510006, China.
  • Levine M; Department of Chemistry, The University of Texas at Austin, Austin, TX 78712-1224.
  • Zou T; Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Science, Sun Yat-Sen University, Guangzhou 510006, China.
  • Sessler JL; Department of Chemistry, The University of Texas at Austin, Austin, TX 78712-1224.
  • Liang H; Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
Proc Natl Acad Sci U S A ; 121(24): e2404668121, 2024 Jun 11.
Article en En | MEDLINE | ID: mdl-38833473
ABSTRACT
Developing anticancer drugs with low side effects is an ongoing challenge. Immunogenic cell death (ICD) has received extensive attention as a potential synergistic modality for cancer immunotherapy. However, only a limited set of drugs or treatment modalities can trigger an ICD response and none of them have cytotoxic selectivity. This provides an incentive to explore strategies that might provide more effective ICD inducers free of adverse side effects. Here, we report a metal-based complex (Cu-1) that disrupts cellular redox homeostasis and effectively stimulates an antitumor immune response with high cytotoxic specificity. Upon entering tumor cells, this Cu(II) complex enhances the production of intracellular radical oxidative species while concurrently depleting glutathione (GSH). As the result of heightening cellular oxidative stress, Cu-1 gives rise to a relatively high cytotoxicity to cancer cells, whereas normal cells with low levels of GSH are relatively unaffected. The present Cu(II) complex initiates a potent ferroptosis-dependent ICD response and effectively inhibits in vivo tumor growth in an animal model (c57BL/6 mice challenged with colorectal cancer). This study presents a strategy to develop metal-based drugs that could synergistically potentiate cytotoxic selectivity and promote apoptosis-independent ICD responses through perturbations in redox homeostasis.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Oxidación-Reducción / Cobre / Glutatión / Homeostasis Límite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Oxidación-Reducción / Cobre / Glutatión / Homeostasis Límite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2024 Tipo del documento: Article País de afiliación: China