Nordentatin Inhibits Neuroblastoma Cell Proliferation and Migration through Regulation of GSK-3 Pathway.

Chantana Boonyarat,Panatchakorn Boonput,Rawiwun Kaewamatawong,Chavi Yenjai,Nantakorn Tongloh,Suchada Chaiwiwatrakul,Pornthip Waiwut

doi:10.3390/cimb44030070

Abstract

Cancer is caused by abnormal cell changes leading to uncontrolled cell growth. The specific characteristics of cancer cells, including the loss of apoptotic control and the ability to migrate into and invade the surrounding tissue, result in cancer cell metastasis to other parts of the body. Therefore, the inhibition of the proliferation, migration, and invasion of cancer cells are the principal goals in the treatment of cancer. This study aimed to investigate the inhibitory activity of nordentatin, a coumarin derivative isolated from Clausena harmandiana, regarding the proliferation and migration of human neuroblastoma cells (SH-SY5Y). Nordentatin at a concentration of 100 µM showed cell cytotoxicity toward SH-SY5Y that was significantly different from that of the control group (p < 0.01) at 24, 48, and 72 h. Moreover, nordentatin inhibited SH-SY5Y proliferation by inhibiting the antiapoptotic protein Mcl-1, leading to the cleavage of caspase-3 and resulting in the inhibition of a migratory protein, MMP-9, through the GSK-3 pathway (compared with cells treated with a GSK inhibitor). These results suggest that nordentatin inhibited the proliferation and migration of neuroblastoma cells through the GSK-3 pathway.

Highlights

Regarding the effect of nordentatin on the protein matrix metalloprotein-9 (MMP-9), which is a proteinase and collagenase, the results indicated that there was clear suppression of matrix metalloproteinases (MMP)-9 expression in the nordentatin test compared to the control group
This study investigated the effect of nordentatin from Clausena harmandiana on SH-SY5Y cancer cell proliferation and migration
It was found that nordentatin inhibited the proliferation and migration of SH-SY5Y cells by inhibiting Glycogen synthase kinase-3 (GSK-3) phosphorylation, which controls the expression of myeloid cell leukemia 1 (Mcl-1), resulting in the activation of cleaved caspase-3 and the apoptosis of cancer cells

Summary

Introduction

Received: 17 January 2022Accepted: 23 February 2022Published: 24 February 2022Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Licensee MDPI, Basel, Switzerland.Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).Cancer is one of the most common diseases in Thailand and throughout the world.As a result of environmental variables and shifting social factors, the incidence rate tends to rise every year. Cancer is also one of the world’s top causes of death. According to the

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