APD-Containing Cyclolipodepsipeptides Target Mitochondrial Function in Hypoxic Cancer Cells.
Cell Chem Biol
; 25(11): 1337-1349.e12, 2018 11 15.
Article
em En
| MEDLINE
| ID: mdl-30122371
ABSTRACT
The natural product family of macrocyclic lipodepsipeptides containing the 4-amido-2,4-pentadienoate functionality possesses intriguing cytotoxic selectivity toward hypoxic cancer cells. These subpopulations of cancer cells display increased metastatic potential and resistance to chemo- and radiotherapy. In this paper, we present studies on the mechanism of action of these natural products in hypoxic cancer cells and show that this involves rapid and hypoxia-selective collapse of mitochondrial integrity and function. These events drive a regulated cell death process that potentially could function as a powerful tool in the fight against chemo- and radiotherapy-resistant cancer cells. Toward that end, we demonstrate activity in two different mouse tumor models.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Depsipeptídeos
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Hipóxia Tumoral
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Mitocôndrias
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Antineoplásicos
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Cell Chem Biol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Dinamarca