2. Academic Validation
  3. Bruceine A induces cell growth inhibition and apoptosis through PFKFB4/GSK3β signaling in pancreatic cancer

Bruceine A induces cell growth inhibition and apoptosis through PFKFB4/GSK3β signaling in pancreatic cancer

  • Pharmacol Res. 2021 Jul:169:105658. doi: 10.1016/j.phrs.2021.105658.
Pengfei Zhang 1,  Weiwei Tao 2,  Cai Lu 3,  Lu Fan 4,  Qihang Jiang 5,  Chengbin Yang 6,  Erxin Shang 7,  Haibo Cheng 8,  Chuntao Che 9,  Jinao Duan 10,  Ming Zhao 11
Affiliations

Affiliations

  • 1 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: zhangpengfei@njucm.edu.cn.
  • 2 School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: tw845@163.com.
  • 3 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: 20183089@njucm.edu.cn.
  • 4 School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: lufan@njucm.edu.cn.
  • 5 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: 20181348@njucm.edu.cn.
  • 6 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: 20190371@njucm.edu.cn.
  • 7 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: shex@njucm.edu.cn.
  • 8 Collaborative Innovation Center of Jiangsu Province of Cancer Prevention and Treatment of Chinese Medicine, Nanjing 210023, China. Electronic address: hbcheng_njucm@163.com.
  • 9 Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA. Electronic address: chect@uic.edu.
  • 10 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: dja@njucm.edu.cn.
  • 11 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: mingzhao@njucm.edu.cn.
PMID: 33992797 DOI: 10.1016/j.phrs.2021.105658
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 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.

Keywords

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (PubChem CID: 2723939); 1-Hydroxybenzotriazole (PubChem CID: 75771); Biotin (PubChem CID: 171548); Bruceine A; Bruceine A (PubChem CID: 160006); Dimethylformamide (PubChem CID: 6228); GSK3β; Glycolysis; N,N-Diisopropylethylamine (PubChem CID: 81531); N-BOC ethylenediamine (PubChem CID: 187201); PFKFB4; Pancreatic cancer; Trifluoroacetic acid (PubChem CID: 6422); dichloromethane (PubChem CID: 6344); tert-butyl bromoacetate (PubChem CID: 79177).

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