Avaliação do potencial antiproliferativo de Lectinas de organismos marinhos frente a células de carcinoma de pulmão humano

Abstract

Cancer is a group of over one hundred diseases characterized by the uncontrolled growth of abnormal cells. A global public health problem, it is the leading cause of death among individuals under 70. Lung cancer is the most common and the leading cause of cancer-related deaths. Lung cancer is categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), which accounts for the majority of cases and is the type least responsive to chemotherapy. From this perspective, the search for new therapeutic alternatives is urgent. The oceans cover a large part of the Earth's surface and are rich in biodiversity. Given their vastness, they are considered a still largely unexplored source of biologically active molecules. In this sense, marine algae lectins possess interesting physicochemical and biological characteristics that make them prime candidates as key agents in cancer diagnosis and/or therapy. This study aimed to evaluate the in vitro antiproliferative potential of lectins isolated from marine organisms, as well as their cytotoxicity profile against normal cells. The MTT colorimetric method was used to assess anticancer activity and determine the IC50. The effect of lectins on cell morphology was also assessed using rapid panoptic staining, and their interference with cell adhesion was also evaluated. Furthermore, in vivo toxicity was evaluated using the Artemia salina model. Among the lectins studied, those extracted from the red algae Solieriafiliformis (SfL, IC50 = 65.6 μg/mL), Amansiamultifida (AML, IC50 = 52.4 μg/mL), and Meristiellaechinocarpa(MEL, IC50 = 134.8 μg/mL) obtained the best results, proving to be more selective for the A549 tumor cell line and presenting reduced toxicity for the healthy murine fibroblast cell line L929. In addition to the cytotoxic effect, the three lectins also promoted morphological changes in the treated cells, as well as interfering with tumor cell adhesion. The mechanism of cell death induction was investigated by flow cytometry. Caspase 3/7 activity was also evaluated. Flow cytometry demonstrated that SfL, AML, and MEL induce apoptosis, as evidenced by double labeling with Annexin V and 7-AAD. However, it was not possible to determine whether apoptosis was caused by caspase 3/7. Finally, in the in vivo toxicity evaluation of Artemia salina, 100% of individuals remained alive at all concentrations tested (500μg/mL - 7.8μg/mL). Thus, it is evident that the tested lectins have an antiproliferative effect against lung carcinoma cells, inducing cell death by apoptosis.