Avaliação da toxicidade da fase vapor do óleo essencial de Thymus vulgaris L. (tomilho) e do timol em fibroblastos e células tumorais de pulmão

Abstract

Essential oils (EO) are a source of compounds with diverse pharmacological activities. Due to their volatility, the components can be directly delivered to the lung tissue by inhalation, an interesting characteristic for the treatment of lung cancer. The aim of this study was to evaluate the cytotoxicity of the vapor phase of the thyme EO and its major compound, thymol, on the lung cancer cells A549 and H292, as well on the MRC-5 line, a non-tumor lung fibroblast model. For this purpose, the thyme EO was acquired commercially and chemical analysis via CG/MS confirmed thymol as the major compound (41.84%). To perform in vitro tests, 1x104 cells/mL were seeded in the 8 central wells of 24-well culture plates and treated for 24, 48, and 72 h with vapor phase of different concentrations of OE (62.5-1000 μg/mL/well) and thymol (31.25-500 μg/mL/well), which were added to the cell-free wells. Cytotoxicity was assessed by MTT reduction and Sulforodamine B staining assays and expressed as concentration capable of generating vapor that causes 50% reduction of cell viability (ICV50). Both OE and thymol were cytotoxic to the three cell lines in a dose dependent manner, however thymol showed greater toxicity. In the 48 h treatments were obtained the ICV50 to A549 cell line of 305 μg/mL/well and 150 μg/mL/well when using OE and thymol, respectively. To H292 cells it was 137.9 and 648 μg/mL/well. The vapor phase of the thymol was less toxic for the non-tumor cells (MRC-5), with the selectivity index (SI) greater than 2 considering the period of 48 h of treatment. To evaluate the synergic cytotoxic effect of thymol with radiation, cells were treated for 6 hours with the compound (31.25-125 μg/mL/well) before exposure to 9 Gray (Gy) of radiation. After 48 hours, cell viability assays were performed. The vapor phase of thymol acted in synergy with the radiation, causing a greater reduction in the viability of tumor cells. The results indicate that the cytotoxicity of the vapor phase of the thyme OE is due mainly to its major compound, thymol, which was more cytotoxic and selective than the OE, being a potential radiosensitizer when used in association with radiation.