Rational design of mitochondria-targeted fluorescent biosensors for in vivo elucidation of the interaction between breast cancer metastasis and mitochondrial autophagy.
Biosens Bioelectron
; 251: 116123, 2024 May 01.
Article
em En
| MEDLINE
| ID: mdl-38359670
ABSTRACT
Breast cancer lung metastases (BCLM) are a major cause of high mortality in patients. The shortage of therapeutic targets and rapid drug screening tools for BCLM is a major challenge at present. Mitochondrial autophagy, which involves the degradation of proteins associated with cancer cell aggressiveness, represents a possible therapeutic approach for the treatment of BCLM. Herein, four fluorescent biosensors with different alkyl chains were designed and synthesized to monitor mitochondrial autophagy. Among them, PMV-12 demonstrated the highest sensitivity to viscosity variance, the least impact on polarity, and the longest imaging time. The introduction of the C12-chain made PMV-12 anchored in the mitochondrial membrane without being disturbed by changes of the mitochondrial membrane potential (MMP), thereby achieving the long-term monitor in situ for mitochondrial autophagy. Mitochondria stained with PMV-12 induced swelling and viscosity increase after treating with apigenin, which indicated that apigenin is a potential mitochondrial autophagy inducer. Apigenin was subsequently verified to inhibit cancer cell invasion by 92%. Furthermore, PMV-12 could monitor the process of BCLM in vivo and evaluate the therapeutic effects of apigenin. This work provides a fluorescent tool for elucidating the role of mitochondrial autophagy in the BCLM process and for anti-metastatic drug development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Técnicas Biossensoriais
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Neoplasias Pulmonares
Limite:
Female
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Humans
Idioma:
En
Revista:
Biosens Bioelectron
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article