Avaliação da toxicidade de polissulfetos de Petiveria alliacea L. em associação à radiação ionizante, em DNA plasmidial e células tumorais

Abstract

The plant Petiveria alliacea L. is traditionally used in folk medicine to treat various diseases and symptoms, including depression, rheumatism, pain, and cancer. Among the polysulfides present in the plant species the dibenzyl trisulfide (DTS) is one of the compounds with numerous reports in the literature with antitumor activity. Cancer is a multifactorial disease that comprises several different types, breast cancer being one of the most frequent in the world, excluding non-melanoma skin cancers, with its own characteristics, manifestations and evolution, including cellular sensitivity that may vary in relation to treatment. Currently, most cancers are treated by multimodal approaches, whether chemotherapy, radiotherapy, and surgery, among others, so that together they act more effectively in oncological treatment. The search for new substances or treatment strategies with antitumor capabilities is current and of interest for the well-being of patients. Therefore, the aim of this study was to evaluate the biological effects of polysulfides: dibenzyl monosulfide (DMS), dibenzyl disulfide (DDS), dibenzyl trisulfide (DTS) and the three polysulfides together (mix) from the species P. alliacea, associated or not with ionizing radiation (IR), in plasmid DNA and in the human breast adenocarcinoma tumor line MCF-7. The genotoxic potential of polysulfides DMS, DDS, DTS and the mix, associated or not with IR, was evaluated using electrophoresis technique for analysis of plasmid DNA conformation in agarose gel. Regarding the assays with the MCF-7 lineage, the cytotoxic potential of polysulfides was evaluated through cell viability tests (Crystal Violet and WST-1). The effect of DTS associated or not with IR was also evaluated through clonogenic recovery assays, migration assay and immunolabeling for γH2AX. The results obtained suggest that polysulfides and the mix confer protection to plasmid DNA. However, the results with the MCF-7 tumor line that only the DTS polysulfide alone caused cytotoxicity, with reduced cell viability. Regarding the assays associated with IR, the polysulfides DMS and DDS did not act as radiomodifiers, protecting or sensitizing the radioinduced effects. However, the DTS associated with IR, in the clonogenic recovery assay, was able to inhibit colony formation, potentiating the effect observed with IR alone. In the migration assay DTS neither stimulated nor inhibited cell migration and the detection of phosphorylated histones (γH2AX) by immunofluorescence showed an increase of double breaks in DNA. These results point out, that unlike DMS and DDS, DTS was able to act as a possible radiosensitizer, increasing the lethal effect when administered in combination with IR.