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. a novel strategy to down-regulate EGFR signaling using the phenolic compound, rosmarinic acid.
RosmarinicActive components of natural foods are increasingly receiving attention for their chemopreventive and chemotherapeutic potential in a wide variety of cancers. One such food component, rosmarinic acid (RA), is a widely distributed phenolic compound in various herbal plants such as rosemary, sweet basil, sage, mint, and perilla (Figure 1) [10,11]. RA is regarded as a daily-consumed safe ingredient, due to its extensive use in the food industry for flavoring, but studies have also elucidated a medicinal role for RA, especially in regard to its anti-oxidant, and anti-inflammatory activities [12,13]. Furthermore, an emerging body of literature has also described the growth inhibitory and anti-invasion properties of RA in colon, skin, breast and ovarian cancers in vitro and/or in vivo [14][15][16][17][18][19], but the mechanisms underlying these effects are poorly understood. A chemopreventive role for RA in HNSCC has been described in 7,12-dimethylbenz (a) anthracene-induced hamster buccal pouch carcinogenesis [20], but a chemotherapeutic role for RA in the treatment of HNSCC has not yet been reported.Given the anti-oxidant properties attributed to RA, it is possible that RA's anti-tumor effects stem from its ability to combat oxidative stress in HNSCC. Oxidative ...