Details

Autor(en) / Beteiligte

• Salkin, Hasan
• Satir-Basaran, Guzide
• Korkmaz, Seyda
• Burcin Gonen, Zeynep
• Erdem Basaran, Kemal

Titel

Mesenchymal stem cell-derived conditioned medium and Methysergide give rise to crosstalk inhibition of 5-HT2A and 5-HT7 receptors in neuroblastoma cells

Ist Teil von

• Brain research, 2023-06, Vol.1808, p.148354-148354, Article 148354

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2023

Quelle

ScienceDirect

Beschreibungen/Notizen

• Neuroblastoma cell lines (BE(2)-Cs) are active in the Gs signal axis via 5-HT7R. When CM and methysergide are applied to BE(2)-Cs, it shifts the Gs signal axis to the Gq signal axis and activation of 5-HT2AR is observed. This crosstalk inhibition of 5-HT7R-5-HT2AR with CM and methysergide induced the apoptosis. The figure was created with biorender.com. [Display omitted] •Methysergide creates crosstalk inhibition between serotonin and adenosin receptors.•MSC secretome and methysergide suppress neuroblastoma cells via 5-HT7R inhibition.•MSC secretome and methysergide combination increase apoptosis in BE(2)-C cell line.•MSC secretome and methysergide combination shift the Gs pathway to Gq pathway. (s): We aimed to investigate the effects of mesenchymal stem cell secretome and methysergide combination on 5-hydroxytryptamine 2A, (5-HT2AR), 5-hydroxytryptamine 7 (5-HT7R), adenosine 2A (A2AR) receptors and CD73 on neuroblastoma cell line and how they affect biological characteristics. Methysergide was used as a serotonin antagonist on the neuroblastoma cells. Human dental pulp-derived stem cells (hDPSCs) used to obtain conditioned medium (CM). Methysergide drug was prepared in CM and applied to neuroblastoma cells. Analysis of 5-HT7R, 5-HT2AR, A2AR and CD73 expressions was performed by western blot and immunofluorescence staining. Total apoptosis, mitochondrial membrane depolarization, Ki-67 proliferation test, viability analysis, DNA damage and cell cycle analysis were performed in accordance with the product procedure by using biological activity test kits. Our results showed that neuroblastoma cancer cells are normally on the Gs signaling axis via the serotonin 7 receptor and the adenosine 2A receptor. CM and Methysergide inhibited the 5-HT7 and A2A receptor levels in neuroblastoma cells. We found that CM and methysergide formed crosstalk inhibition between 5-HT2AR, 5-HT7R, A2AR and CD73. CM and Methysergide increased the total apoptosis in neuroblastoma cells and induced the mitochondrial membrane depolarization. CM and Methysergide induced the DNA damage and arrested in G0/G1 phase of cell cycle of the neuroblastoma cells. These findings suggest that the combination of CM and methysergite may exert a therapeutic effect on neuroblastoma cancer cells, and future in vivo studies may be important in area of neuroblastoma research to support the findings.