Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway
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Jiwei Wang1, Qichao Qi1, Zichao Feng1, Xin Zhang1, Bin Huang1, Anjing Chen1, Lars Prestegarden2,3, Xingang Li1, Jian Wang1,2
1Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, P.R. China
2Department of Biomedicine, University of Bergen, 5009 Bergen, Norway
3Department of Dermatology, University of Bergen, 5021 Bergen, Norway
Xingang Li, email: [email protected]
Jian Wang, email: [email protected]
Keywords: berberine, glioblastoma, autophagy, apoptosis, metabolism
Received: March 15, 2016 Accepted: August 09, 2016 Published: August 19, 2016
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.
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