ABSTRACT
The purpose of the current study was to develop and test a theoretical model that could explain the mechanism of action of gallic acid (GA) in the oral squamous cell carcinoma context for the first time. The theoretical model was developed using bioinformatics and interaction network analysis to evaluate the effect of GA on oral squamous cell carcinoma. In a second step to confirm theoretical results, migration, invasion, proliferation, and gene expression (Col1A1, E-cadherin, HIF-1α, and caspase-3) were performed under normoxic and hypoxic conditions. Our study indicated that treatment with GA resulted in the inhibition of cell proliferation, migration, and invasion in neoplastic cells. Observation of the molecular mechanism showed that GA upregulates E-cadherin expression and downregulates Col1A1 and HIF-1α expression, suggesting that GA might be a potential anticancer compound. In conclusion, the present study demonstrated that GA significantly reduces cell proliferation, invasion, and migration by increasing E-cadherin and repressing Col1A1.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Squamous Cell/drug therapy , Gallic Acid/pharmacology , Models, Biological , Mouth Neoplasms/drug therapy , Cadherins/metabolism , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Caspase 3/metabolism , Cell Hypoxia , Cell Line, Tumor/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Collagen Type I/metabolism , Collagen Type I, alpha 1 Chain , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Neoplasm InvasivenessABSTRACT
We compared the richness and abundance of free-feeding herbivore insects (sap-sucking and leaf-chewing), leaf herbivory damage, leaf toughness and total phenolic content between two ontogenetic stages (juvenile and reproductive) of Handroanthus spongiosus (Rizzini) S. O. Grose (Bignoniaceae) throughout the rainy season in a Brazilian seasonally dry tropical forest. Twenty marked individuals of H. spongiosus were sampled per ontogenetic stage in each period of the rainy season (beginning, middle, and end). Herbivore richness and abundance did not differ between ontogenetic stages, but higher percentage of leaf damage, higher concentration of phenolic compounds, and lower leaf toughness were observed for juvenile individuals. The greatest morphospecies abundance was found at the beginning of the rainy season, but folivory increment was higher at the end, despite the fact that leaf toughness and total phenolic content increased in the same period. No significant relationships between leaf damage and both total phenolic content and leaf toughness were observed. These results suggest that insect richness and abundance do not track changes in foliage quality throughout plant ontogeny, but their decrease along rainy season confirms what was predicted for tropical dry forests. The general trends described in the current study corroborate those described in the literature about herbivores and plant ontogeny. However, the lack of relationship between herbivore damage and the two plant attributes considered here indicates that the analyses of multiple defensive traits (the defense syndrome) must be more enlightening to determine the mechanisms driving temporal and spatial patterns of herbivore attack.
