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Open AccessArticle

FAK and S6K1 Inhibitor, Neferine, Dually Induces Autophagy and Apoptosis in Human Neuroblastoma Cells

1
Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam
2
Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Shoufeng, Hualien 97401, Taiwan
3
Neural Regeneration Laboratory, Taipei Veterans General Hospital, Taipei 11260, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Marco Guerrini
Molecules 2018, 23(12), 3110; https://doi.org/10.3390/molecules23123110
Received: 4 November 2018 / Revised: 24 November 2018 / Accepted: 25 November 2018 / Published: 28 November 2018
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
Human neuroblastoma cancer is the most typical extracranial solid tumor. Yet, new remedial treatment therapies are demanded to overcome its sluggish survival rate. Neferine, isolated from the lotus embryos, inhibits the proliferation of various cancer cells. This study aimed to evaluate the anti-cancer activity of neferine in IMR32 human neuroblastoma cells and to expose the concealable molecular mechanisms. IMR32 cells were treated with different concentrations of neferine, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability. In an effort to determine the molecular mechanisms in neferine-incubated IMR32 cells, cell cycle arrest, cell migration, and focal adhesion kinase (FAK), the 70-kDa ribosomal S6 kinase 1 (S6K1), poly (ADP-ribose) polymerase (PARP), caspase-3, Beclin-1, and microtubule-associated protein 1A/1B-light chain 3 (LC3) protein expressions were investigated. Neferine strongly disrupted the neuroblastoma cell growth via induction of G2/M phase arrest. Furthermore, neferine provoked autophagy and apoptosis in IMR32 cells, confirmed by p-FAK, and p-S6K1 reduction, LC3-II accumulation, Beclin-1 overexpression, and cleaved caspase-3/PARP improvement. Finally, neferine markedly retarded cell migration of neuroblastoma cancer cells. As a result, our findings for the first time showed an explicit anti-cancer effect of neferine in IMR32 cells, suggesting that neferine might be a potential candidate against human neuroblastoma cells to improve clinical outcomes with further in vivo investigation. View Full-Text
Keywords: neferine; FAK/S6K1; autophagy; apoptosis; human neuroblastoma cells neferine; FAK/S6K1; autophagy; apoptosis; human neuroblastoma cells
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Pham, D.-C.; Chang, Y.-C.; Lin, S.-R.; Fuh, Y.-M.; Tsai, M.-J.; Weng, C.-F. FAK and S6K1 Inhibitor, Neferine, Dually Induces Autophagy and Apoptosis in Human Neuroblastoma Cells. Molecules 2018, 23, 3110.

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