Avaliação citotóxica de derivados glicosídicos da lausona em linhagens tumorais

Abstract

Cancer is a disease characterized by the abnormal growth of cells that can invade other tissues and spread to other organs, representing a major public health issue. One of the main challenges in cancer treatment is the low selectivity of the chemotherapeutic agents currently used, highlighting the need to investigate new compounds. Lawsone, a plant-derived product, has shown cytotoxic effects in different tumor cell lines, and chemical modifications to its structure can lead to more potent derivatives. Additionally, anomeric isomer derivatives exhibit similar chemical structures, differing only in the orientation of the anomeric carbon, which may influence their biological properties. Therefore, the aim of this study was to evaluate the cytotoxic activity of two anomeric derivatives of lawsone, APSO-5 and APSO-19, in lung carcinoma (A549), melanoma (B16-F10), and glioma (C6) cell lines. The cytotoxicity of the lawsone derivatives, as well as of lawsone itself, was assessed using the Sulforhodamine B assay in the tumor cell lines to determine the IC50 and select the most responsive cell line for subsequent experiments. The results showed that both compounds exhibited cytotoxic effects in all tested cell lines, with IC50 values below 12 μM. The A549 cell line was selected for further experiments, as lung carcinoma is the most prevalent and deadly type of cancer, making the identification of promising therapeutic compounds particularly relevant. The clonogenic assay demonstrated that both compounds reduced colony formation in A549 cells. Furthermore, APSO-19 was found to inhibit cell migration after 24 hours of treatment. Fluorescence assays using DAPI and Phalloidin/FITC revealed morphological changes in A549 cells treated with the derivatives, such as cytoplasmic shrinkage, cell rounding, and the presence of apoptotic bodies. It was also observed that higher concentrations of APSO-19 induced ROS production in A549 cells. Finally, none of the studied compounds showed toxicity toward human erythrocytes. In conclusion, the anomeric glycosidic derivatives of lawsone demonstrated strong cytotoxic effects in the tested cell lines and exhibited distinct biological activities, with APSO-19 showing greater ROS induction and inhibition of migration capacity in A549 cells.