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Meriolin1 induces cell cycle arrest, apoptosis, autophagy and targeting the Akt/MAPKs pathways in human neuroblastoma SH-SY5Y cells.

Authors
  • Su, Dan1
  • Wang, Wenbin2
  • Wu, Xinyue2
  • Li, Minyue2
  • Yan, Xuelong2
  • Hua, Zhonghong2
  • Liu, Jiahui2
  • Zhu, Zhiyu2
  • Hu, Kun2
  • Ren, Jie2
  • 1 Changzhou No.2 People's Hospital, Changzhou, Jiangsu, China. , (China)
  • 2 School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, Jiangsu, China. , (China)
Type
Published Article
Journal
The Journal of pharmacy and pharmacology
Publication Date
Apr 01, 2020
Volume
72
Issue
4
Pages
561–574
Identifiers
DOI: 10.1111/jphp.13224
PMID: 32034768
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Meriolins, a kind of chemical hybrid between meridianins and variolins, have lately been determined as kinase inhibitors and reportedly have antitumour activity. However, there is currently no in-depth study for the action mechanism. This study aimed to elucidate the potentially antitumour action mechanism of Meriolin1 on human neuroblastoma (SH-SY5Y) cells. Firstly, cell viability was detected by MTT assay. Secondly, cell cycle, cell apoptosis, cell autophagy, reactive oxygen species and mitochondrial membrane potential (ΔΨm) were measured by flow cytometry. Then, cell cycle-associated proteins, Bcl-2 family proteins, Akt/MAPK proteins and autophagy-associated proteins expressions were evaluated by Western blot. Bcl-2 and Bax mRNA expressions were also evaluated by qRT-PCR. Furthermore, cell adhesion assay and Hoechst 33258 fluorescent staining were carried out to detect the effect of Meriolin1 on cell adhesion and morphology. Finally, to gain further insight into mechanism of action of Meriolin1 to CDK protein, the molecular docking study was performed by using the CDOCKER module of DS software. Meriolin1 could exert the antitumour activity on SH-SY5Y cells by inducing cell cycle arrest, cell autophagy, the mitochondrion-dependent cell apoptosis and targeting the Akt/MAPKs signalling pathway. Meriolin1 might be a promising therapeutic candidate for neuroblastoma. © 2020 Royal Pharmaceutical Society.

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