ReferenceID 1341
Bruceine A induces cell growth inhibition and apoptosis through PFKFB4/GSK3β signaling in pancreatic cancer
Pharmacol Res
Pancreatic cancer is one of the most aggressive cancers with a poor prognosis and 5-year low survival rate. In the present study, we report that bruceine A, a quassinoid found in Brucea javanica (L.) Merr. has a strong a
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Record Fields
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- Reference Id
- 1341
- Evidence Id
- 17931
- Core Evidence Id
- 17931
- Source Reference Id
- 2750
- Herb2 Reference Id
- HBREF003547
- Subject Paper Key
- HBIN018905_33992797
- Pubmed Id
- 33992797
- Doi
- 10.1016/j.phrs.2021.105658
- Paper Title
- Bruceine A induces cell growth inhibition and apoptosis through PFKFB4/GSK3β signaling in pancreatic cancer
- Paper Abstract
- Pancreatic cancer is one of the most aggressive cancers with a poor prognosis and 5-year low survival rate. In the present study, we report that bruceine A, a quassinoid found in Brucea javanica (L.) Merr. has a strong antitumor activity against human pancreatic cancer cells both in vitro and in vivo. Human proteome microarray reveals that 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is the candidate target of bruceine A and both fluorescence measurement and microscale thermophoresis suggest bruceine A binds to PFKFB4. Bruceine A suppresses glycolysis by inhibiting PFKFB4, leading to cell cycle arrest and apoptosis in MIA PaCa-2 cells. Furthermore, glycogen synthase kinase-3 beta (GSK3beta) is identified as a downstream target of PFKFB4 and an PFKFB4-interacting protein. Moreover, bruceine A induces cell growth inhibition and apoptosis through GSK3beta, which is dysregulated in pancreatic cancer and closely related to the prognosis. In all, these findings suggest that bruceine A inhibits human pancreatic cancer cell growth via PFKFB4/GSK3beta-mediated glycolysis, and it may serve as a potent agent for curing human pancreatic cancer.
- Journal
- Pharmacol Res
- Publish Year
- 2021
- Experiment Subject
- human; merr.; mia paca-2 cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Cancers; Bruceine; Pancreatic Cancer
- Paper Title Cn
- Paper Title En
- Bruceine A induces cell growth inhibition and apoptosis through PFKFB4/GSK3β signaling in pancreatic cancer
- Bilingual Status
- semi_complete