Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 883, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2020.173366
Keywords
Diosmetin; CML; SKP2; Bcr-Abl; Apoptosis
Categories
Funding
- National Natural Science Foundation of China [81670156, 81773213]
- Natural Science Foundation research team of Guangdong Province [2018B030312001]
- Innovative Academic Team of Guangzhou Education System [1201610014]
- Research Team of Department of Education of Guangdong Province [2017KCXTD027]
- Guangzhou key medical discipline construction project fund
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Bcr-Abl is the primary cause as well as currently key therapeutic target of chronic myeloid leukemia (CML). SKP2, an E3 ligase, is a downstream factor of Bcr-Abl to motivate the cell cycle transition of CML and also found to bind and activate Bcr-Abl in reverse. Therefore, SKP2/Bcr-Abl pathway is an attractive target for CML treatment. This study aims to identify an inhibitor of the SKP2/Bcr-Abl pathway based on a large screening of the natural products. We demonstrate that Diosmetin, a kind of phytoestrogens, notably downregulates the expression of SKP2, Bcr-Abl phosphorylation, and moderately downregulates the Bcr-Abl level. Furthermore, Diosmetin displays a favorable anti-tumor activity in CML cells and xenograft models. Collectively, our study reveals a natural compound in the treatment of CML on the basis of SKP2/Bcr-Abl signaling pathway.
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