Journal article
Apigenin suppresses migration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expression
Toxicology and applied pharmacology, Vol.272(1), pp.108-116
10/01/2013
DOI: 10.1016/j.taap.2013.05.028
PMCID: PMC3823051
PMID: 23743303
Abstract
Environmental exposure to arsenic is known to cause various cancers. There are some potential relationships between cell malignant transformation and C-X-C chemokine receptor type 4 (CXCR4) expressions. Metastasis, one of the major characteristics of malignantly transformed cells, contributes to the high mortality of cells. CXCR4 and its natural chemokine ligand C-X-C motif ligand 12 (CXCL12) play a critical role in metastasis. Therefore, identification of nutritional factors which are able to inhibit CXCR4 is important for protection from environmental arsenic-induced carcinogenesis and for abolishing metastasis of malignantly transformed cells. The present study demonstrates that apigenin (4′,5,7-trihydroxyflavone), a natural dietary flavonoid, suppressed CXCR4 expression in arsenic-transformed Beas-2B cells (B-AsT) and several other types of transformed/cancer cells in a dose- and time-dependent manner. Neither proteasome nor lysosome inhibitor had any effect in reducing the apigenin-induced down-regulation of CXCR4, indicating that apigenin-induced down-regulation of CXCR4 is not due to proteolytic degradation. The down-regulation of CXCR4 is mainly due to the inhibition of nuclear factor κB (NF-κB) transcriptional activity. Apigenin also abolished migration and invasion of transformed cells induced by CXCL12. In a xenograft mouse model, apigenin down-regulated CXCR4 expression and suppressed tumor growth. Taken together, our results show that apigenin is a novel inhibitor of CXCR4 expression. This dietary flavonoid has the potential to suppress migration and invasion of transformed cells and prevent environmental arsenic-induced carcinogenesis.
•Apigenin has a potential in preventing environmental arsenic induced carcinogenesis.•Apigenin suppresses CXCR4 in malignant transformed cells in vitro and in vivo.•The down-regulation of CXCR4 is mainly due to inhibition of NF-κB activity.
Details
- Title: Subtitle
- Apigenin suppresses migration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expression
- Creators
- Lei Wang - University of KentuckyLisha Kuang - University of KentuckyJohn Andrew Hitron - University of KentuckyYoung-Ok Son - University of KentuckyXin Wang - University of KentuckyAmit Budhraja - University of KentuckyJeong-Chae Lee - University of KentuckyPoyil Pratheeshkumar - University of KentuckyGang Chen - University of KentuckyZhuo Zhang - University of KentuckyJia Luo - University of KentuckyXianglin Shi - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Toxicology and applied pharmacology, Vol.272(1), pp.108-116
- DOI
- 10.1016/j.taap.2013.05.028
- PMID
- 23743303
- PMCID
- PMC3823051
- NLM abbreviation
- Toxicol Appl Pharmacol
- ISSN
- 0041-008X
- eISSN
- 1096-0333
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 10/01/2013
- Academic Unit
- Pathology
- Record Identifier
- 9984201113202771
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