Research on the Effect of Amino Acid Substitution of Cyclosaplin Peptide in Breast Cancer Cell Line (MDA-MB-231) and in a Human Leukemia Cell Line (K562)

Abstract: It was the aim of this study to develop Cyclosaplin analogues and assess the anticancer effects of those peptide analogues on both MDA-MB-231 and K562 cell lines. The analogues of Cyclosaplin peptide (Cyclosaplin-2A and Cyclosaplin-7G) were designed and then investigated by online web server predictor AntiCP. The peptide analogues were applied to MDA-MB-231 and K562 cells in various concentrations and for various periods of time. The anticancer potential was confirmed by the MTT assay. Haemolytic activity also was assessed. In order to investigate the apoptotic effects of peptides on cancer cells, different tests such as morphological examination, Giemsa test, and DNA fragmentation were performed. Lactate dehydrogenase leakage assay was used to reject peptide-induced necrosis. As a result of computational studies, we discovered that the analogues of peptides also have anticancer properties. However, we have found through our practical research that analogues had less anticancer properties than their parent peptides. The MTT assay and morphological study confirmed the anticancer effects. For MD-AMB-231 cells, an IC50 of Cyclosaplin-2A was 70 µg/mL, and Cyclosaplin-7G was 90 µg/mL. In addition, for K562 cells, an IC50 of Cyclosaplin-2A was 10 µg/mL, and Cyclosaplin-7G was 15 µg/mL. Other tests also confirmed the anticancer effect of the peptide analogues. According to haemolytic assays, none of the peptide analogues possessed any haemolytic activity against human erythrocytes, indicating that the compounds are non-toxic to normal cells. There was evidence that peptide analogues, particularly Cyclosaplin-2A, had anticancer properties against cells derived from breast (MDA-MB-231) and blood (K562) cancers. © 2022, Allerton Press, Inc.