Ciclopirox platinum(IV) conjugates suppress tumors by promoting mitophagy and provoking immune responses.

Autor: Li S; Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, PR China., Feng S; Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, PR China., Chen Y; Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, PR China; Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China., Sun B; Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, PR China., Zhang N; Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, PR China., Zhao Y; Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, PR China., Han J; Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, PR China; Liaocheng High-Tech Biotechnology Co., Ltd, Liaocheng 252059, PR China., Liu Z; Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, PR China., He YQ; Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, PR China., Wang Q; Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, PR China. Electronic address: lywqp@126.com.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2024 Nov; Vol. 260, pp. 112696. Date of Electronic Publication: 2024 Aug 11.
DOI: 10.1016/j.jinorgbio.2024.112696
Abstrakt: Mitophagy is an important target for antitumor drugs development. A series of ciclopirox (CPX) platinum(IV) hybrids targeting PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitophagy were designed and prepared as antitumor agents. The dual CPX platinum(IV) complex with cisplatin core was screened out as a candidate, which displayed promising antitumor activities both in vitro and in vivo. Mechanistically, it caused serious DNA damage in tumor cells. Then, remarkable mitochondrial damage was induced accompanied by the mitochondrial membrane depolarization and reactive oxygen species generation, which further promoted apoptosis through the Bcl-2/Bax/Caspase3 pathway. Furthermore, mitophagy was ignited via the PINK1/Parkin/P62/LC3 axis, and exhibited positive influence on promoting the apoptosis of tumor cells. The antitumor immunity was boosted by the block of immune check point programmed cell death ligand-1 (PD-L1), which further increased the density of T cells in tumors. Subsequently, the metastasis of tumor cells was inhibited by inhibiting angiogenesis in tumors.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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