Abstract
This study aimed to investigate, in oral squamous carcinoma cells (OSCC), the antineoplastic effect of Apis mellifera honey produced from Aroeira and wildflower, in the region of Jequitinhonha River Valley, Brazil. Furthermore, we investigate the molecular mechanism of honey performance through bioinformatic analysis. Honey and OSCC-related gene list were screened using GeneCards. The online tool STRING was used to identify the potential interaction networks of protein products of these genes. The genes with the highest weighted number of links (WNL) were called leader genes. GO and KEGG pathway analysis was performed to classify the genes. We use a search tool STITCH for interactions of chemicals-proteins. The chemical characterization of honey and its antiproliferative and antimigratory effects in SCC-9 cell lines was evaluated in vitro. The analysis of the interaction network obtained from the STRING database indicated by the following leader genes: TNF, IL6 and HDAC1. GO analysis for the honey, and OSCC-related proteins revealed that leader genes-regulated cancers genes were markedly enriched in some functions. Through the chemical characterization, the bioactive classes: steroids/triterpenoids, flavonoids, saponins, alkaloids, and tannins were identified. Polyphenols act in activating CASP3 and TP53 and inhibit the action of DNMT1. The honey produced from Aroeira and wildflower reduced proliferative phenotype and migration of OSCC cells. Key words: Aroeira honey, Myracrodruon urundeuva, wild honey, Apis mellifera, therapeutic, Jequitinhonha River Valley.  
Highlights
Honey is a product that presents characteristics of the bees that originate it and has botanicogeographical characteristics from the geographic area which it was produced
The TNF, IL6 and HDAC1 genes showed a large number of interactions
The bioinformatics analyzes conducted in the present study showed that the performance of honey in Oral Squamous Cell Carcinoma (OSCC) is dominated by the leader genes TNF, IL-6, and HDAC1
Summary
Honey is a product that presents characteristics of the bees that originate it and has botanicogeographical characteristics from the geographic area which it was produced. The honey processed from the nectar of flowers and/or saccharinic secretions of other species carries inheritance of the plant species of origin. Among these inheritances are some bioactive properties resulting from secondary metabolism in plant species Santos el al. Oral Squamous Cell Carcinoma (OSCC) represents a worldwide public health problem, due to the high prevalence rates but mainly due to the survival rates, morbidity, and mortality associated with the disease (Petersen, 2005). The great knowledge of the science about the etiopathogenesis of the disease does not, correspond to the improvement in the prognosis and treatment of the individuals affected (Day et al, 2003; Bramer et al, 2009)
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