Melatonin inhibits osteosarcoma stem cells by suppressing SOX9-mediated signaling

Melatonin (N-acetyl-5-methoxytryptamine) has been reported to suppress epithelial-mesenchymal transition and cancer stem cells in some types of cancer. However, the effects of melatonin on the osteosarcoma stem cells, epithelial-mesenchymal transition and metastasis of osteosarcoma are still not cle...

Full description

Saved in:
Bibliographic Details
Published in:Life sciences (1973) 2018-08, Vol.207, p.253-264
Main Authors: Qu, Hao, Xue, Yue, Lian, Wenwen, Wang, Cong, He, Jia, Fu, Qihong, Zhong, Lijia, Lin, Nong, Lai, Lihua, Ye, Zhaoming, Wang, Qingqing
Format: Article
Language:English
Subjects:
Biomedical materials
Bone cancer
Cancer
Cancer stem cells
Melatonin
Metastasis
Osteosarcoma
Signaling
SOX9
Stem cells
Tumors
Wound healing
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Melatonin (N-acetyl-5-methoxytryptamine) has been reported to suppress epithelial-mesenchymal transition and cancer stem cells in some types of cancer. However, the effects of melatonin on the osteosarcoma stem cells, epithelial-mesenchymal transition and metastasis of osteosarcoma are still not clear. The present study was conducted to dissect the activity of melatonin on the osteosarcoma stem cells and the underlying mechanisms. MTT, wound healing, transwell assay and western blotting were conducted to determine the effect of melatonin on osteosarcoma cell invasion and migration and downregulation of SOX9-mediated signaling. Tumor spheroid assay and FACS analysis were performed to analyze the inhibition of the osteosarcoma stem cells. In vivo model for tumor formation and metastasis from single cell clone was used to evaluate the suppression of osteosarcoma stem cells by melatonin. We demonstrated that melatonin potently suppresses the migration and invasion of osteosarcoma cells. Furthermore, melatonin significantly inhibits the sarcosphere formation of osteosarcoma stem cells and regulates EMT markers of osteosarcoma cells. In vivo mice model showed that melatonin significantly inhibits the initiation and metastasis of osteosarcoma. SOX9 is the key transcription factor mediating the effect of melatonin. Melatonin inhibited of cancer stem cell by down-regulation of SOX9-mediated signaling pathway in osteosarcoma. Collectively, these results deepen the understanding of the biological functions of melatonin and provide new insights for the intervention of osteosarcoma stem cells.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2018.04.030