title: Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway.
abstract: There is an urgent need for new therapeutic strategies for patients with glioblastoma multiforme (GBM). Previous studies have shown that berberine (BBR), a natural plant alkaloid, has potent anti-tumor activity. However, the mechanisms leading to cancer cell death have not been clearly elucidated. In this study, we show that BBR has profound effects on the metabolic state of GBM cells, leading to high autophagy flux and impaired glycolytic capacity. Functionally, these alterations reduce the invasive properties, proliferative potential and induce apoptotic cell death. The molecular alterations preceding these changes are characterized by inhibition of the AMPK/mTOR/ULK1 pathway. Finally, we demonstrate that BBR significantly reduces tumor growth in vivo, demonstrating the potential clinical benefits for autophagy modulating plant alkaloids in cancer therapy.
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, P.R. China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, P.R. China.
authors.forename: Qichao
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, P.R. China.
authors.forename: Zichao
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, P.R. China.
authors.forename: Anjing
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Biomedicine, University of Bergen, 5009 Bergen, Norway.|Department of Dermatology, University of Bergen, 5021 Bergen, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Prestegarden
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, P.R. China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, P.R. China.|Department of Biomedicine, University of Bergen, 5009 Bergen, Norway.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D000071189:Autophagy-Related Protein-1 Homolog / Q000187:drug effects / Q000378:metabolism; D001599:Berberine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047908:Intracellular Signaling Peptides and Proteins; D001599:Berberine; C546842:MTOR protein, human; D000071189:Autophagy-Related Protein-1 Homolog; D058570:TOR Serine-Threonine Kinases; C484754:ULK1 protein, human; D055372:AMP-Activated Protein Kinases
keywords: apoptosis; autophagy; berberine; glioblastoma; metabolism