Inhibition of focal adhesion kinase/paxillin axis by caffeic acid phenethyl ester restrains aggressive behaviors of head and neck squamous cell carcinoma in vitro.

Objective: Caffeic acid phenethyl ester (CAPE), one of the components of propolis that is produced by honeybees, reportedly suppresses multiple diseases, including bacterial infection, inflammation, and cancer. We aimed to investigate the inhibitory effects of CAPE on epithelial-mesenchymal transition (EMT) status and aggressive behaviors of human head and neck squamous cell carcinoma (HNSCC) in vitro and the underlying signaling pathway.

Design: To examine the cell growth and in vitro tumorigenic potential of HNSCC cells, cell viability and soft agar colony formation assays, respectively, were performed. Transwell migration and invasion assays were conducted to monitor HNSCC cells' aggressive behaviors. Western blotting and immunocytochemistry analyses were done to investigate the signaling pathway responsible for relieving EMT progression and HNSCC cell aggressiveness.

Results: CAPE inhibited the in vitro tumorigenic potential of SNU-1041 cells stimulated by epidermal growth factor and suppressed the migratory and invasive capacities of SNU-1041 cells, irrespective of their cell proliferation state. CAPE was, at least partially, capable of inhibiting EMT progression by upregulating E-cadherin expression, which was accompanied by the reduction of phosphorylated focal adhesion kinase (FAK) and Paxillin. The inhibition of the FAK/Paxillin axis by PF-562271 was sufficient to alleviate the EMT progression through the induction of E-cadherin and aggressive behaviors of SNU-1041 cells.

Conclusions: CAPE has a therapeutic potential as an anti-metastatic drug candidate for HNSCC therapy targeting the FAK/Paxillin axis.