Berberine-induced autophagic cell death by elevating GRP78 levels in cancer cells
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Xiaoqin La1,*, Lichao Zhang1,2,*, Zhuoyu Li1, Peng Yang1, Yingying Wang1
1Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China
2School of Life Science, Shanxi University, Taiyuan 030006, China
*These authors have contributed equally to this work
Zhuoyu Li, email: [email protected]
Keywords: berberine, autophagy, cancer cell death, GRP78, VPS34
Received: May 13, 2016 Accepted: January 10, 2017 Published: February 01, 2017
Berberine, an isoquinoline alkaloid extracted from Coptidis Rhizoma, has been shown to induce cancer cell autophagic death. Glucose regulated protein 78 (GRP78) is associated with stress-induced autophagy. However, the related mechanisms between berberine-induced cancer cell autophagy and GRP78 remain to be elucidated. Here, we report that berberine can induce autophagic cancer cell death by elevating levels of GRP78. These results further demonstrated that berberine enhanced GRP78 by suppression of ubiquitination / proteasomal degradation of GRP78 and activation of ATF6. Moreover, fluorescence spectrum assay revealed that berberine could bind to GRP78 and form complexes. Finally, co-IP analysis showed that the ability of GRP78 to bind to VPS34 was increased with berberine treatment. Taken together, our results suggest that berberine induces autophagic cancer cell death via enhancing GRP78 levels and the ability of GRP78 to bind to VPS34.
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