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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 ...

To retrospectively analyze local and systemic factors that resulted in the short-term tooth loss of teeth that were previously assigned a favorable prognosis in patients who were seen and treated over an observational five-year period. This retrospective study included the records of patients who had a minimum of two dental exams at least twelve months apart over a 5-year period. This study investigated extracted teeth with an initially favorable periodontal prognosis that were then divided into one of four categories based on the reason for extraction: caries, periodontal disease, endodontic reasons, or fracture. Patient- and tooth-related factors associated with the extracted teeth were recorded: crown-to-root ratio, initial pocket depth, initial periodontal diagnosis, maintenance interval, presence of existing restoration, furcation involvement, and systemic conditions. Data analysis was performed using a linear mixed model. A total of 50 patients with 111 teeth met the inclusion criteria for this study. A higher odds ratio (OR) for tooth loss due to caries, endodontic reasons, and fracture were found in teeth with a history of root canal treatment with an OR of 3.61, 3.86, and 2.52, respectively. For tooth loss due to periodontal disease, higher ORs were found in patients who were on anti-depressants (OR = 4.28) and patients who had an initial diagnosis of Stage III/IV periodontitis (OR = 2.66). In addition, teeth with initial probing depths ≥5 mm (OR = 4.32) and with furcation involvement (OR = 1.93) showed a higher OR for tooth loss due to periodontal disease. Within the limitations of this study, previously root-canal-treated teeth present a higher OR for early loss due to caries, recurrent endodontic lesions, or fracture. In addition, patients with anti-depressant medication use, sporadic maintenance, initial probing depths ≥5 mm, and furcation involvement represent a significantly higher OR of tooth loss due to periodontal disease even for initially favorable teeth.