Ainsliadimer A induces ROS-mediated apoptosis in colorectal cancer cells via directly targeting peroxiredoxin 1 and 2.
Cell Chem Biol
; 30(3): 295-307.e5, 2023 03 16.
Article
em En
| MEDLINE
| ID: mdl-36889312
ABSTRACT
The peroxiredoxin (PRDX) family is a class of antioxidant enzymes with peroxidase activity. Human PRDXs currently have six members (PRDX1-6), which are gradually becoming potential therapeutic targets for major diseases such as cancer. In this study, we reported ainsliadimer A (AIN), a sesquiterpene lactone dimer with antitumor activity. We found that AIN directly targets Cys173 of PRDX1 and Cys172 of PRDX2 and then inhibits their peroxidase activities. As a result, the level of intracellular ROS increases, causing oxidative stress damage in mitochondria, inhibiting mitochondrial respiration, and significantly inhibiting ATP production. AIN inhibits the proliferation and induces apoptosis of colorectal cancer cells. Additionally, it inhibits tumor growth in mice and the growth of tumor organoid models. Therefore, AIN can be one of the natural compounds targeting PRDX1 and PRDX2 in the treatment of colorectal cancer.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Peroxirredoxinas
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article