Licochalcone A Inhibits BDNF and TrkB Gene Expression and Hypoxic Growth of Human Tumor Cell Lines

Hypoxic cellular proliferation is a common feature of tumor cells and is associated with tumor progression. Therefore, the inhibition of hypoxic cellular proliferation is expected to regulate malignancy processes. Licochalcone A (LicA) is known to show inhibitory effects on cell growth in normoxia,...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2020-01, Vol.21 (2), p.506
Main Authors: Arita, Michitsune, Koike, Junichi, Yoshikawa, Nobuji, Kondo, Motonari, Hemmi, Hiromichi
Format: Article
Language:English
Subjects:
AKT protein
bdnf/trkb
Brain-derived neurotrophic factor
Cancer
Cell growth
Cell proliferation
Cervix
Colorectal cancer
Colorectal carcinoma
Gene expression
Glyceraldehyde-3-phosphate dehydrogenase
human established cell lines
Hypoxia
Investigations
Kinases
Licochalcone A
Ligands
Malignancy
Medical prognosis
Metabolism
Metastasis
Neuroblastoma
Neurotrophin 4
Proteins
Transcription
transcriptional inhibitor
TrkB receptors
Tropomyosin
Tumor cell lines
Tumor cells
Tumors
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:Hypoxic cellular proliferation is a common feature of tumor cells and is associated with tumor progression. Therefore, the inhibition of hypoxic cellular proliferation is expected to regulate malignancy processes. Licochalcone A (LicA) is known to show inhibitory effects on cell growth in normoxia, but it is unclear whether LicA exerts similar effects in hypoxia. Here, we studied the inhibitory activity of LicA in the hypoxic cellular proliferation of tumor cells and its molecular mechanism using human cell lines derived from various tumors including neuroblastoma and colorectal cancer. LicA inhibited cell growth at a 50% inhibitory concentration between 7.0 and 31.1 µM in hypoxia. LicA significantly suppressed hypoxic induction of tropomyosin receptor kinase B ( ) gene expression at the transcription level. LicA also downregulated mRNA levels of the TrkB high-affinity ligand brain-derived neurotrophic factor, but not neurotrophin-4, another TrkB ligand, or glyceraldehyde-3-phosphate dehydrogenase, indicating that the inhibitory activity of LicA is selective. Since both LicA-treatment and -knockdown decreased activation of protein kinase B in hypoxia, LicA exerts its inhibitory effect against hypoxic cell growth through inhibition of the TrkB-AKT axis. These results suggest that LicA has therapeutic potential for malignant tumors including neuroblastoma and colorectal cancer.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms21020506