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Open AccessArticle

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

1
Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan
2
Department of Surgery, Toho University School of Medicine, Tokyo 143-8540, Japan
3
Cokey Systems, Co., Ltd., Tokyo 102-0075, Japan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 506; https://doi.org/10.3390/ijms21020506
Received: 27 December 2019 / Revised: 7 January 2020 / Accepted: 10 January 2020 / Published: 13 January 2020
(This article belongs to the Special Issue Bioactive Phytochemicals for Cancer Prevention and Treatment II)
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 (TrkB) 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 TrkB-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. View Full-Text
Keywords: BDNF/TrkB; hypoxia; licochalcone A; human established cell lines; transcriptional inhibitor BDNF/TrkB; hypoxia; licochalcone A; human established cell lines; transcriptional inhibitor
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Arita, M.; Koike, J.; Yoshikawa, N.; Kondo, M.; Hemmi, H. Licochalcone A Inhibits BDNF and TrkB Gene Expression and Hypoxic Growth of Human Tumor Cell Lines. Int. J. Mol. Sci. 2020, 21, 506.

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