Inhibition of Sirtuin 6 Induces Neuroblastoma Differentiation

Song, Ha Yong; Rellinger, Eric J.; Park, Seong Hoon; Paul, Pritha; Qiao, Jingbo; Vasilopoulos, Athanasios; Özden, Özkan; Gius, David; Chung, Dai H.

doi:10.21873/anticanres.12268

Cited by 9 publications

(4 citation statements)

References 24 publications

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“…Thus, it is crucial to develop antineuroblastoma drugs by considering growth inhibition and differentiation induction effects simultaneously, but differentiation therapy presents many difficulties in heterogeneous solid tumors. PHOX2B, MYCN, and TRK have been previously reported as the target associated with neuroblastoma differentiation; , we also notice that some proliferation-related targets, including HDAC, − EZH2, and MEK, have been demonstrated to participate in the differentiation process on neuroblastoma cells. Therefore, gaining insight into the common mechanisms of neuroblastoma differentiation and proliferation may provide opportunities for developing appropriate target inhibitors that have promising treatment consequences.…”

Section: Introductionsupporting

confidence: 51%

Discovery of Novel Oxazepine Derivatives as Akt/ROCK Inhibitors for Growth Arrest and Differentiation Induction in Neuroblastoma Treatment

Che,

Bing,

et al. 2023

J. Med. Chem.

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Patients with high-risk neuroblastoma face limited treatment choices, typically involving a combination of cytotoxic and differentiation maintenance therapies due to a scarcity of drugs. Evidence suggests that targeted inhibitors may provide opportunities for inducing neuroblastoma differentiation while inhibiting proliferation. Here, we demonstrate the synergistic effect of inhibiting Akt and ROCK in antineuroblastoma and present the design and discovery of a new Akt/ROCK inhibitor, B12. It displays strong antiproliferative effects and excellent differentiation inducing activity against Neuro2a cells. Treatment with B12 results in the arrest of G0/G1 cell cycles, a significant decrease in N-myc protein level, and an increase in differentiation markers. The administration of B12 effectively suppresses xenograft tumor growth and promotes differentiation. Overall, the discovery of B12 based on the Akt/ROCK dual inhibition strategy may provide hope for the development of more effective and targeted therapies for this challenging disease.

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Section: Introductionsupporting

confidence: 51%

Discovery of Novel Oxazepine Derivatives as Akt/ROCK Inhibitors for Growth Arrest and Differentiation Induction in Neuroblastoma Treatment

Che,

Bing,

et al. 2023

J. Med. Chem.

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“…SIRT6 is a member of the SIRTs and mainly exists in the nucleus [11]. Increasingly evidence indicates that SIRTs play an important role in various differentiation processes by promoting or inhibiting many signaling pathways [12,13]. SIRT6 is expressed in both bone marrow stroma cells and bone-related cells in mouse and human models.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effect of Sirtuin6 (SIRT6) on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

et al. 2019

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BackgroundThe imbalance between bone resorption and formation is the basic mechanism underlying osteoporosis in the elderly. Osteogenesis is the differentiation of human mesenchymal stem cells (hMSCs) into osteoblasts. Sirtuin6 (SIRT6) regulates various biological functions, including differentiation. Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a non-selective cation channel that can be activated by physical and chemical stimulation. However, experimental data supporting the role of SIRT6 in osteogenic differentiation (OD) of hMSCs are lacking.Material/MethodsDifferentiation of hMSCs was induced. The expressions of SIRT6, TRPV1, and CGRP were detected by Q-PCR, Western blot, and ELISA, respectively. SIRT6 was overexpressed in hMSCs by transfection. ALP activity and Alizarin Red staining were utilized to detect the effect of SIRT6 on hMSC OD. Then, capsaicin and capsazepine, the TRPV1 agonist and antagonist, respectively, were administrated to assess the role of TRPV1.ResultsSIRT6 expression was downregulated during hMSC differentiation. SIRT6 overexpression was accompanied by reduced expression of specific genes and alkaline phosphatase (ALP) activity in osteoblasts. Furthermore, TRPV1 channel was also reduced by SIRT6 overexpression via ubiquitinating TRPV1. Capsaicin was utilized in SIRT6-overexpressed cells. Capsaicin therapy counteracted the effect of SIRT6 overexpression on OD, and markedly decreased OD.ConclusionThe SIRT6-TRPV1-CGRP signal axis is the key to regulating OD in hMSCs, which could be a potential therapeutic target for osteoporosis and bone loss-related diseases.

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“…From the system described above, experiments were performed using cell cultures in biomedical labs with the N2A cell line. This is a neuroblastom cell line from albino rats, employed in basic reseach on neural signaling, axon regeneration, nervous system connection repair [ 22 ], and also in chemotherapy [ 23 ]. For the purpose of illustration, a subset of the obtained output oscillation signals was selected considering different cell occupation rates.…”

Section: Resultsmentioning

confidence: 99%

Remote Cell Growth Sensing Using Self-Sustained Bio-Oscillations

Pérez

Huertas

Olmo

et al. 2018

Sensors

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A smart sensor system for cell culture real-time supervision is proposed, allowing for a significant reduction in human effort applied to this type of assay. The approach converts the cell culture under test into a suitable “biological” oscillator. The system enables the remote acquisition and management of the “biological” oscillation signals through a secure web interface. The indirectly observed biological properties are cell growth and cell number, which are straightforwardly related to the measured bio-oscillation signal parameters, i.e., frequency and amplitude. The sensor extracts the information without complex circuitry for acquisition and measurement, taking advantage of the microcontroller features. A discrete prototype for sensing and remote monitoring is presented along with the experimental results obtained from the performed measurements, achieving the expected performance and outcomes.

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Inhibition of Sirtuin 6 Induces Neuroblastoma Differentiation

Abstract: Abstract. Background/Aim: Sirtuins (SIRTs)

Cited by 9 publications

References 24 publications

Discovery of Novel Oxazepine Derivatives as Akt/ROCK Inhibitors for Growth Arrest and Differentiation Induction in Neuroblastoma Treatment

Discovery of Novel Oxazepine Derivatives as Akt/ROCK Inhibitors for Growth Arrest and Differentiation Induction in Neuroblastoma Treatment

Inhibitory Effect of Sirtuin6 (SIRT6) on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

Remote Cell Growth Sensing Using Self-Sustained Bio-Oscillations

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