Efeito citotóxico do derivado indólico NM-01-28-22 em linhagem de carcinoma de pulmão

Abstract

Lung cancer is a neoplasm with a high mortality and incidence rate. The main treatments for lung cancer are chemotherapy, radiotherapy, and surgery, depending on the stage of the cancer in the patient. Chemotherapy is the most widely used therapeutic practice, but it has limitations due to adverse effects caused by its low systemic selectivity for normal cells compared to tumor cells. Many studies have demonstrated the importance of indoles and their derivatives in cancer research. Thus, indole and its derivatives allow for greater selectivity for tumor cells. Our study aims to evaluate the indole derivative NM-01-28-22 in cell inhibition in tumor cell lines and its cytotoxic effect on the lung carcinoma cell line. Initially, the compound was tested against cell lines to determine the most susceptible to the derivative. For this purpose, the Sulforhodamine B assay was used to evaluate the degree of inhibition of the NM-01-28-22 derivative in the three cell lines A549 (lung cancer), PC-3 (prostate cancer), and MCF-7 (breast cancer). For cytotoxicity assays in the A549 cell line, cell migration, clone formation, morphological alterations by DAPI and Phalloidin-Fitc staining, mitochondrial membrane potential by rhodamine 123 dye, and ROS production by the DCFH-DA probe were performed. Toxicity in human erythrocytes was verified by the hemolysis assay. In the analysis of the degree of inhibition, the values of the 50% inhibitory concentration (IC50) of the compound were obtained in the A549 (6.5 µM), MCF-7 (17.5 µM), and PC-3 (16.2 µM) cell lines. Given that the indolic derivative showed a low IC50 in A549 cells and considering its relevance in epidemiology, this cell line was used in subsequent cytotoxicity assays. The derivative inhibited cell migration and clone formation in A549 cells at all three concentrations. The derivative also induced loss of mitochondrial membrane potential and ROS production, suggesting cell death by apoptosis. The morphological changes evidenced by treatment with the derivative also show cell death in the A549 cell line. The derivative was tested at high concentrations in human erythrocytes and no toxic effect was observed. These results show that the derivative inhibited cell growth in three distinct tumor cell lines. It also showed a high cytotoxic effect in the A549 cell line without showing a toxic effect in human erythrocytes.