Berberine induces neuronal differentiation through inhibition of cancer stemness and epithelial-mesenchymal transition in neuroblastoma cells

Challagundla, Naveen; Gaikwad, Sagar; Agrawal-Rajput, Reena

doi:10.1016/j.phymed.2016.03.013

Cited by 77 publications

(47 citation statements)

References 30 publications

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Section: Discussionmentioning

confidence: 99%

“…A previous study demonstrated that berberine, a plant alkaloid, induces neuronal differentiation accompanied by increases in differentiation markers such as MAP2, TUBB3 and NCAM in N2a cells. 47 Additionally, TLR4 plays a key role in activating NF-κB-mediated effects to trigger the differentiation of glioblastoma stem-like cells. 48,49 HA (100 μg/mL) synthesized by HAS3 is a main component of the brain extracellular matrix, and effectively triggers the TLR4-NF-κB pathway in differentiating glioblastoma stemlike cells.…”

Section: Discussionmentioning

confidence: 99%

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Melatonin promotes neuroblastoma cell differentiation by activating hyaluronan synthase 3‐induced mitophagy

et al. 2019

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Neuroblastoma is the second most common pediatric malignancy and has a high rate of spontaneous remission. Uncovering the mechanisms underlying neuroblastoma cell differentiation is critical for therapeutic purposes. A neuroblastoma cell line (N2a) treated with either serum withdrawal (<2.5%) or melatonin (>0.1 nmol/L) for 24 hours was used as a cell differentiation research model. Interestingly, the hyaluronan synthase 3 (HAS3) protein was induced in differentiated N2a cells. N2a‐allografted nude mice received an intraperitoneal injection of melatonin (40 or 80 mg/kg/day for 3 weeks). The mean tumor volume in mice treated with 80 mg/kg melatonin was smaller than that in PBS‐treated mice (1416.3 and 3041.3 mm 3 , respectively, difference = 1625 mm 3 , * P = 0.0003, n = 7 per group). Compared with the vector control group, N2a cells with forced HAS3 overexpression showed significantly increased neuron length (* P = 0.00082) and neurite outgrowth (* P = 0.00059). Intracellular changes in autophagy, including distorted mitochondria with abnormal circular inner membranes, were detected by transmission electron microscopy (TEM). Our study demonstrated that HAS3‐mediated signaling activated by physiological concentrations of melatonin (>0.1 nmol/L) triggered significant N2a cell differentiation. These results provide molecular data with potential clinical relevance for therapeutic drug development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Melatonin promotes neuroblastoma cell differentiation by activating hyaluronan synthase 3‐induced mitophagy

et al. 2019

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“…Berberis, decreased the expression of the mesenchymal markers vimentin and ibronectin and restored the epithelial marker E-cadherin, thereby contributing to the reversal of EMT [85].…”

Section: Anti-vimentin Agentsmentioning

confidence: 96%

Targeting the Cytoskeleton with Plant-Bioactive Compounds in Cancer Therapy

Ardelean¹

2017

Cytoskeleton - Structure, Dynamics, Function and Disease

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In this overview we describe the main plant-derived bioactive compounds used in cancer therapy which has the cell cytoskeleton as therapeutic target. Three major classes of these compounds are described: antimitotics with microtubule-destabilizing and-stabilizing efects, plant-bioactive compounds that interact with intermediate ilaments/actin, and plant-bioactive compounds that interact with intermediate ilaments like keratins and vimentin. We also focus on the molecular aspects of interactions with their cellular targets: microtubules, intermediate ilaments, and microilaments. Some critical aspects of cardiac side efects of cancer chemotherapy are also discussed, focusing on cardiac cytoskeleton and protective efect of plant-derived compounds. The application of plant bioactives in the treatment of cancer has resulted in increased therapeutic eicacy through targeting the cytoskeleton, respectively, prevention of the injury of cytoskeletal components elicited by chemotherapeutics.

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“…These results suggest that a NC progenitor cell can become cancerous with only a few genetic modifications. Meanwhile, neuroblastoma treated with the drug berberine, which has recently been implicated in inhibiting cell proliferation (Ortiz et al, 2014), demonstrates increased expression of terminally differentiated neuronal markers and decreased expression of stem cell markers (Naveen et al, 2016). These results could suggest that some pediatric cancers such as neuroblastoma may retain potency from earlier stages in development to become tumorigenic.…”

Section: Potency Induction and Specification Of Neural Crest Andmentioning

confidence: 99%

Neural crest and cancer: Divergent travelers on similar paths

Gallik

Treffy

Nacke

et al. 2017

Mechanisms of Development

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Neural crest cells are multipotent progenitors that dynamically interpret diverse microenvironments to migrate significant distances as a loosely associated collective and contribute to many tissues in the developing vertebrate embryo. Uncovering details of neural crest migration has helped to inform a general understanding of collective cell migration, including that which occurs during cancer metastasis. Here, we discuss several commonalities and differences of neural crest and cancer cell migration and behavior. First, we focus on some of the molecular pathways required for the initial specification and potency of neural crest cells and the roles of many of these pathways in cancer progression. We also describe epithelial-to-mesenchymal transition, which plays a critical role in initiating both neural crest migration and cancer metastasis. Finally, we evaluate studies that demonstrate myriad forms of cell-cell and cell-environment communication during neural crest and cancer collective migration to highlight the remarkable similarities in their molecular and cell biological regulation.

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Berberine induces neuronal differentiation through inhibition of cancer stemness and epithelial-mesenchymal transition in neuroblastoma cells

Cited by 77 publications

References 30 publications

Melatonin promotes neuroblastoma cell differentiation by activating hyaluronan synthase 3‐induced mitophagy

Melatonin promotes neuroblastoma cell differentiation by activating hyaluronan synthase 3‐induced mitophagy

Targeting the Cytoskeleton with Plant-Bioactive Compounds in Cancer Therapy

Neural crest and cancer: Divergent travelers on similar paths

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