Análise do efeito antitumoral do óleo essencial de Cymbopogon densiflorus sobre células de câncer de bexiga.
2018
Bladder carcinoma is the world's twentieth most common cancer. Its conventional treatment involves chemotherapy using the MVAC protocol (methotrexate, vinblastine, doxorubinc and cisplatin) which has many toxic effects by targeting not only tumor cells but also healthy cells. Thereby, it is need for new research in search of compounds with potential antitumor effect appears. The essential oil of Cymbopogon densiflorus, popularly known as "holy grass", presents several biological activities, but its antitumor activity was not studied. The aim of this study was to analyze the antitumor effect of the essential oil of C. densiflorus on the RT4 and T24 cell lines of bladder cancer that present different TP53 gene status. Thus, the oil was extracted by hydrodistillation and the gas chromatography method coupled to the mass spectrometry (GC-MS) was used for the characterization of the major compounds. These compounds and their potential biological activities and mechanisms of action related to cancer were analyzed in silico. Then, cytotoxicity and cell proliferation were analyzed after treatment with the essential oil of C. densiflorus, as well as analysis of its effect on cell cycle modulation and the apoptosis process. In the characterization of the oil, five major compounds were identified: trans-p-mentha-2,8-dien-1-ol, cis-p-mentha-2,8-dien-1-ol, trans-p- mentha (7), 8-dien-2-ol, cis-piperitol and cis-p-mentha-1 (7), 8-dien-2-ol. The in silico analysis of these indicated the antitumor activity of the essential oil C. densiflorus by different mechanisms, mainly as caspase 8 stimulant, increased TP53 gene expression, inhibition of the JAK2 gene and as agonist of apoptosis, besides the inhibition of MMP9. The essential oil of C. densiflorus presented cytotoxic effect and reduced the cellular proliferation of RT4 and T24. There was no modulation in the cell cycle of the RT4 and T24 lines after treatment. In the RT4 line, apoptosis rates were increased after the treatment. In the T24 line there was no increase in apoptosis or necrosis, suggesting that other cell death pathways are occurring in this line. In conclusion, the essential oil of C. densiflorus shows cytotoxic activity in bladder tumor lines, probably inducing mechanisms related to apoptosis in wild TP53 strains.
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