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Rosmarinic Acid Inhibits Cell Growth and Migration in Head and Neck Squamous Cell Carcinoma Cell Lines by Attenuating Epidermal Growth Factor Receptor Signaling

Abstract

Zohra Tumur, Carlos Guerra, Peter Yanni, Ahmad Eltejaye, Christi Waer, Tursun Alkam and Bradley S Henson

Objective: Active components of natural foods are increasingly receiving attention for their chemopreventive and chemotherapeutic potential in a wide variety of cancers. Rosmarinic acid (RA), a phenolic compound in various herbal plants, is well-recognized for its anti-oxidant, anti-inflammatory, anti-proliferative properties in a variety of cell types. In this report, we describe a novel role for RA as an inhibitor of epidermal growth factor (EGF) stimulated signaling in HNSCC and propose a cellular reactive oxygen species (ROS)-mediated mechanism for the observed effects.

Methods: Cellular growth, migration and reactive oxygen species (ROS) profiles were examined in RA-treated and untreated HNSCC cell lines (UM- SCC-6 and UM-SCC-10B) using the WST-1 viability assay, established in vitro migration assays, and the CM-H2DCFDA ROS assay, respectively. The influence of RA on EGF-stimulated phosphorylation and its downstream pathways was evaluated using Western-blotting techniques.

Results: RA inhibited cell viability, migration and cellular production of ROS in HNSCC cell lines. Furthermore, RA inhibited EGF-induced phosphorylation of the EGFR at tyrosine residues 992 and 845, which led to downregulation of the phosphatidylinositol 3-kinase Akt (PI3K/Akt) and mitogen-activated protein kinase ERK (MAPK/ ERK) pathways.

Conclusions: This is the first report describing both growth- and motility-inhibitory roles for RA in HNSCC cells. Additionally, our study is the first to demonstrate that treatment with RA can reduce EGF-induced activation of PI3K/ Akt in tumor cells. The present data suggests that RA holds promise as a chemotherapeutic agent against HNSCC.