Estudo do efeito de compostos da semente de Persea americana sobre as proteínas oncogênicas VacA e CagA de Helicobacter pylori
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Data
2025-10-28
Autores
Nunes, Amanda Cavalcante Gonzaga
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Universidade Federal do Espírito Santo
Resumo
Gastric cancer is one of the most prevalent and lethal types of cancer. Its development is strongly associated with Helicobacter pylori infection. The bacterium expresses virulence factors such as cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA), which induce various cellular changes, such as inhibition of pro apoptotic signaling, cell cycle dysregulation and increased release of inflammatory interleukins, characterizing them as the main oncogenic proteins of H. pylori. In this context, the present study evaluated the effect of the hydroalcoholic extract of Persea americana (avocado) seeds in vitro and its secondary metabolites in silico on the gene expression of CagA and VacA. The broth microdilution technique was used to determine the minimum inhibitory concentration, with evaluation of the minimum bactericidal concentration on blood agar. Changes in gene expression were assessed by RT-qPCR. The chemical profile of the extract was determined by high-resolution mass spectrometry. Molecular docking studies were conducted between the extract compounds and the RNA and protein structures of CagA and VacA. The extract exhibited bacteriostatic effects starting at 64 µg/mL and bactericidal effects starting at 128 µg/mL. Treatment with the extract significantly reduced cagA and vacA expression by 82.4% and 73.9% after 3h and by 76.5% and 67.1% after 6h, respectively. Fatty acid derivatives (such as avocadene and persenones), organic acids (quinic and malic), and phenolic compounds (chlorogenic acid) were proposed in the extract. Molecular docking results indicated persenones A, B, and C, and persin, as the ligands most likely to interact with the RNA structures, highlighting the most favorable complexes between domain 4 of cagA and persenone C and domain 1 of vacA and persenone A, due to a higher number of predicted hydrogen bonds. Docking with the CagA protein indicated persenone A as the most promising molecule for inhibiting the interaction between CagA and ASPP2, suggesting its potential to modulate molecular pathways associated with H. pylori-induced carcinogenesis. Predictions for the VacA protein indicated stable complexes, but the lack of consensus between programs and experimental data limits the reliability of the predictions. Based on these results, the relevance of avocado seed extract and its bioactive compounds in combating H. pylori and modulating its carcinogenic mechanisms is evident
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Helicobacter pylori , cagA , vacA , Persea americana