title: Apigenin suppresses migration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expression.
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.
authors.affiliation: Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Lisha
authors.initials: L
authors.lastname: Kuang
authors.forename: John Andrew
authors.initials: JA
authors.lastname: Hitron
authors.forename: Young-Ok
authors.initials: YO
authors.lastname: Son
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Amit
authors.initials: A
authors.lastname: Budhraja
authors.forename: Jeong-Chae
authors.initials: JC
authors.lastname: Lee
authors.forename: Poyil
authors.initials: P
authors.lastname: Pratheeshkumar
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Luo
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009361:Neoplasm Invasiveness / Q000473:pathology*; D010957:Plasmids / Q000235:genetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000187:drug effects; D014162:Transfection; D014945:Wound Healing / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D016328:NF-kappa B; D019718:Receptors, CXCR4; D047310:Apigenin; D008156:Luciferases
keywords: Apigenin; CXCL12; CXCR4; Metastasis; Transformed cell