Cytotoxicity and apoptotic-inducing effect of 1-(1-tosyl-1H-indol-3yl)propan-1-one against lung cancer cells

Abstract

Background Lung cancer is the most prevalent and deadly cancer in the world. In the search for new antineoplastic drugs, research into derivatives of natural products revealed the constant evolution of science to provide treatments with fewer adverse effects. Indole is a natural compound found in plants and microorganisms with proven antitumor activity. Modifications to its structure can potentiate its cytotoxic effect on tumor cells. Thus, the aim of this study was to evaluate the cytotoxic potential of the synthetic indole derivative 1-(1-tosyl-1H-indol-3-yl)propan-1-one in tumor cell lines. Methods Sulforhodamine B (SRB) was used to evaluate the cytotoxic effect of compound 1-(1-tosyl-1H-indol-3-yl)propan-1-one against lung cancer (A549), breast cancer (MCF7) and prostate cancer (PC-3) cell lines. Furthermore, the hemolysis assay was carried out on human erythrocytes. The clonogenic and wound healing assays were used to analyze the reduction in colony formation and the migratory capacity of the A549 cell line, respectively. DAPI and Phalloidin/FITC were used to observe morphological changes. Death by apoptosis and necrosis were assessed by flow cytometer. Results The highest inhibitory effect was observed in the A549 cell line, with an IC₅₀ of 2.6 µM. The A549 cell line was further selected for additional biological tests, considering the IC₅₀ and the epidemiological relevance of this cancer. No hemolytic activity was observed in human erythrocytes after exposure to 1-(1-tosyl-1H-indol-3-yl)propan-1-one. In the colony formation test, clone inhibition was observed in the A549 cell line at a concentration of 5.2 µM. In the migration analysis, we observed that the compound inhibited wound closure in the A549 cells at the highest concentrations after 48 h of treatment. In addition, morphological changes characteristic of apoptosis, such as cytoplasmic reduction and changes in the disposition of actin filaments, were observed in the A549 cell line by staining with DAPI and phalloidin/FITC dyes. These results corroborate the flow cytometry results, which showed that the treatment induced apoptosis in the A549 cells. Conclusions Our results showed that the compound 1-(1-tosyl-1H-indol-3-yl)propan-1-one inhibited cell growth, migration and colony formation and promote cell death via apoptosis in A549 cell line.