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Introduction
Cell adhesion molecules are cellular surface proteins involved in binding with other cells or with the extracellular matrix (ECM) in a process called cell adhesion. These molecules play a critical role in the inflammatory response and tumor progression, which promotes cancer-defining biological processes such growth, survival, migration, and metastasis. Therefore, cell adhesion molecule expression is essential for maintaining cell homeostasis. Among the cell adhesion molecules, intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) are constitutively expressed on airway endothelial and epithelial barriers during inflammation, which may play a key role in the recruitment and infiltration of leukocytes across the blood vessels at sites of airway inflammation (1–3). ICAM-1 and VCAM-1 have been shown to be upregulated in vascular cells by several pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) (4–6).
Nuclear factor-κB (NF-κB) is a well-known transcription factor that regulates the expression of cell adhesion molecules and the development of inflammatory responses by upregulating inflammatory mediators (7,8). Previous reports suggest that TNF-α activates the NF-κB signaling pathway, which results in the upregulation of cell adhesion molecules, including ICMA-1 and VCAM-1 (9,10). Inhibition of NF-κB activation induces the suppression of TNF-α-induced ICAM-1 and VCAM-1 mRNA and protein expression levels (11). Therefore, NF-κB, the central regulator in adhesion molecule expression, is a more effective target for anti-inflammatory therapy.
Generally regarded as safe, natural compounds have been shown to have antitumor, anti-angiogenic and anti-inflammatory effects against several cell types (12). Butein (3,3,2′,4′-tetrahydroxychalcone) is a biologically active polyphenol compound derived from numerous plants including the stembark of cashews (Semecarpus anacardium), the heartwood of Dalbergia odorifera, and the traditional Chinese medicinal herbs Caragana jubata and Rhus verniciflua Stokes. Several studies have reported its anti-carcinogenic activities by inhibiting the proliferation of a wide variety of tumor cells (13). Butein can induce growth inhibition through G2/M phase arrest in hepatic cells (14). Butein induces apoptosis through the suppression of STAT-3 gene expression (13) and the sensitization of human hepatoma cells to TRAIL-induced apoptosis via DR5 upregulation and promote NF-κB inactivation (15). Recently, it has been reported that butein inhibits the expression of CXC chemokine receptor-4 (CXCR4), a mediator of the growth and metastasis of tumors, and thus has the potential to suppress cancer metastasis (16).
Despite...