胰腺癌
细胞凋亡
癌症研究
葛兰素史克-3
细胞生长
生物
糖原合酶
细胞生物学
细胞周期
癌症
化学
激酶
内科学
内分泌学
医学
生物化学
糖原
作者
Pengfei Zhang,Weiwei Tao,Lu Cai,Lu Fan,Qihang Jiang,Chengbin Yang,Erxin Shang,Haibo Cheng,Chun‐Tao Che,Jin‐Ao Duan,Ming Zhao
标识
DOI:10.1016/j.phrs.2021.105658
摘要
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 β (GSK3β) is identified as a downstream target of PFKFB4 and an PFKFB4-interacting protein. Moreover, bruceine A induces cell growth inhibition and apoptosis through GSK3β, 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/GSK3β-mediated glycolysis, and it may serve as a potent agent for curing human pancreatic cancer.
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