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

Abstract

Abstract Objectives 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. Methods 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. Key findings 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. Conclusions Meriolin1 might be a promising therapeutic candidate for neuroblastoma.