Abstract
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.
Highlights
Neuroblastoma (NB) is the most common malignant nervous system tumor in babies and the third-most common cancer in children, accounting for ~8% of childhood cancers and 15% of all pediatric cancer deaths [1]
NeferineNeferine is a bis-benzylisoquinoline alkaloid, alkaloid, which is isolated from seed embryos of lotus plant, has been shown for its inhibitory which is isolated from seed embryos of lotus plant, has been shown for its inhibitory effectseffects on the on the proliferation of livercells, cancer cells, lung cells, cancerand cells, and osteosarcoma cells [8,25,26]
We proved that neferine treatment dramatically decreased the protein levels of p-focal adhesion kinase (FAK) and p-S6 kinase 1 (S6K1) in IMR32 human neuroblastoma cells
Summary
Neuroblastoma (NB) is the most common malignant nervous system tumor in babies and the third-most common cancer in children, accounting for ~8% of childhood cancers and 15% of all pediatric cancer deaths [1]. Even though some newborns can recuperate spontaneously, many of those damaged have poor prognosis and aggressive tendency of metastasis [2]. Ongoing treatment used in the administration of neuroblastoma includes surgery, chemotherapy, radiotherapy, and biotherapy. Like cyclophosphamide, doxorubicin, and etoposide show low potency with numerous side effects because the low penetrations of blood brain barrier (BBB) resulted in low bioavailability. It has been shown that neuroblastoma gets resistance to cytotoxic drugs due to stable genetic alterations occurring during treatment [4]. Effective and safe drugs are high-priority required
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