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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.

SUBMITTER: Wang J

PROVIDER: S-EPMC5341849 | biostudies-other | 2016 Oct

REPOSITORIES: biostudies-other

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Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway.

Wang Jiwei J Qi Qichao Q Feng Zichao Z Zhang Xin X Huang Bin B Chen Anjing A Prestegarden Lars L Li Xingang X Wang Jian J

Oncotarget 20161001 41

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 inv ...[more]

PMID: 27557493

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Project description:Salvia chinensia Benth. (Shijianchuan in Chinese, SJC) has been used as a traditional anti-cancer herb. SJC showed good anti-esophageal cancer efficacy based on our clinical application. However, the current research on SJC is minimal, and its anti-cancer effect lacks scientific certification. This study aims to clarify the inhibitory effect of SJC on esophageal cancer and explore its underlying mechanism. Q-Orbitrap high-resolution LC/MS was used to identify the primary chemical constituents in SJC. Cell proliferation and colony formation assays showed that SJC could effectively inhibit the growth of esophageal tumor cells in vitro. To clarify its mechanism of action, proteomic and bioinformatic analyses were carried out by combining tandem mass labeling and two-dimensional liquid chromatography-mass spectrometry (LC-MS). The results indicated that SJC could activate AMPK signaling pathway and effectively promote autophagy in esophageal cancer cells. Therefore, we further used WB to confirm that SJC activated autophagy in esophageal cancer cells through the AMPK / ULK1 signaling pathway. The results showed that P-AMPK and P-ULK1 were significantly up-regulated after the treatment with SJC. The ratio of autophagosomes marker proteins LC3II/I was significantly increased. In addition, the expression of the autophagy substrate protein P62 decreased with the degradation of autophagosomes. Using lentiviral transfection of fluorescent label SensGFP-StubRFP-LC3 protein and revalidation of LC3 expression before and after administration by laser confocal microscopy. Compared with the control group, the fluorescence expression of the SJC group was significantly enhanced, indicating that it promoted autophagy in esophageal cancer cells. Cell morphology and the formation of autophagosomes were observed by transmission electron microscopy. Our study shows that the tumor suppressor effect of SJC is related to promoting autophagy in esophageal tumor cells via the AMPK/ULK1 signaling pathway.

Dataset Information

Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway.

Publications

Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway.

Similar Datasets

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