Ursolic acid-piperazine-dithiocarbamate ruthenium(II) polypyridyl complexes induced necroptosis in MGC-803 cells.
Metallomics
; 14(10)2022 10 11.
Article
em En
| MEDLINE
| ID: mdl-36149330
ABSTRACT
Three ursolic acid-piperazine-dithiocarbamate ruthenium(II) polypyridyl complexes Ru1-Ru3 were designed and synthesized for evaluating antitumor activity. All the complexes exhibited high in vitro cytotoxicity against MGC-803, T24, HepG2, CNE2, MDA-MB-231, MCF-7, A549, and A549/DDP cell lines. Ru1, Ru2, and Ru3 were 11, 8 and 10 times, respectively, more active than cisplatin against A549/DDP. An in vivo study on MGC-803 xenograft mouse models demonstrated that representative Ru2 exhibited an effective inhibitory effect on tumor growth, showing stronger antitumor activity than cisplatin. Biological investigations suggested that Ru2 entered MGC-803 cells by a clathrin-mediated endocytic pathway, initially localizing in the lysosomes and subsequently escaping and localizing in the mitochondria. Mitochondrial swelling resulted in vacuolization, which induced vacuolation-associated cell death and necroptosis with the formation of necrosomes (RIP1-RIP3) and the uptake of propidium iodide. These results demonstrate that the potential of Ru2 as a chemotherapeutic agent to kill cancer cells via a dual mechanism represents an alternative way to eradicate apoptosis-resistant forms of cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rutênio
/
Complexos de Coordenação
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Metallomics
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China