Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
Arch Oral Biol. 2023 Feb;146:105611. doi: 10.1016/j.archoralbio.2022.105611. Epub 2022 Dec 24.
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.
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.
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.
CAPE has a therapeutic potential as an anti-metastatic drug candidate for HNSCC therapy targeting the FAK/Paxillin axis.
咖啡酸苯乙酯（CAPE）是蜜蜂产生的蜂胶的成分之一，据报道可抑制多种疾病，包括细菌感染、炎症和癌症。我们旨在研究 CAPE 对体外人头颈部鳞状细胞癌（HNSCC）上皮-间充质转化（EMT）状态和侵袭行为的抑制作用及其潜在的信号通路。
为了研究 HNSCC 细胞的细胞生长和体外致瘤潜能，分别进行了细胞活力和软琼脂集落形成测定、Transwell 迁移和侵袭测定来监测 HNSCC 细胞的侵袭行为。通过 Western blot 和免疫细胞化学分析来研究负责缓解 EMT 进展和 HNSCC 细胞侵袭性的信号通路。
CAPE 抑制了表皮生长因子刺激的 SNU-1041 细胞的体外致瘤潜能，并抑制了 SNU-1041 细胞的迁移和侵袭能力，而与细胞增殖状态无关。CAPE 至少部分通过上调 E-钙粘蛋白表达抑制 EMT 进展，同时伴随着磷酸化粘着斑激酶（FAK）和桩蛋白的减少。PF-562271 抑制 FAK/桩蛋白轴足以通过诱导 E-钙粘蛋白和 SNU-1041 细胞的侵袭行为来缓解 EMT 进展。
CAPE 具有作为针对 FAK/桩蛋白轴的 HNSCC 治疗的抗转移药物候选物的治疗潜力。
