1. Cytostatic Activity of Sanguinarine and a Cyanide Derivative in Human Erythroleukemia Cells Is Mediated by Suppression of c-MET/MAPK Signaling.
- Author
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Xu X, Deng L, Tang Y, Li J, Zhong T, Hao X, Fan Y, and Mu S
- Subjects
- Humans, Phosphatidylinositol 3-Kinases metabolism, Cyanides, Apoptosis, Proto-Oncogene Proteins c-akt metabolism, Cell Line, Tumor, Cytostatic Agents pharmacology, Leukemia, Erythroblastic, Acute drug therapy, Leukemia drug therapy
- Abstract
Sanguinarine ( 1 ) is a natural product with significant pharmacological effects. However, the application of sanguinarine has been limited due to its toxic side effects and a lack of clarity regarding its molecular mechanisms. To reduce the toxic side effects of sanguinarine, its cyanide derivative ( 1a ) was first designed and synthesized in our previous research. In this study, we confirmed that 1a presents lower toxicity than sanguinarine but shows comparable anti-leukemia activity. Further biological studies using RNA-seq, lentiviral transfection, Western blotting, and flow cytometry analysis first revealed that both compounds 1 and 1a inhibited the proliferation and induced the apoptosis of leukemic cells by regulating the transcription of c-MET and then suppressing downstream pathways, including the MAPK, PI3K/AKT and JAK/STAT pathways. Collectively, the data indicate that 1a , as a potential anti-leukemia lead compound regulating c-MET transcription, exhibits better safety than 1 while maintaining cytostatic activity through the same mechanism as 1 .
- Published
- 2023
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