Bioinformatic and Molecular Interaction Studies Uncover That CCA-1.1 and PGV-1 Differentially Target Mitotic Regulatory Protein and Have a Synergistic Effect against Leukemia Cells

Abstract

CCA-1.1, a modified compound from PGV-1, inhibits tumor cell growth in breast and colorectal cancer. Here, we used bioinformatic and molecular interaction approaches to ascertain the potential activity of CCA-1.1 in targeting leukemia and applied the cytotoxic test in leukemia cells. Genomic data were collected from the Catalogue of Somatic Mutations in Cancer database by using the gene sets from K562 cells as a model for chronic myelogenous leukemia (CML). We identified CCA-1.1 and PGV-1 predicted targets through SwissTargetPrediction. The overlapping genes among CCA-1.1, PGV-1, and K562 cells were chosen for further analysis. We narrowed down the potential targets by using the list of genes involved in cell cycle and mitosis collected through GeneCards. Molecular docking study was performed to determine the molecular interaction of CCA-1.1 or PGV-1 with the predicted protein target. We carried out a cytotoxic test using trypan blue exclusion assay. We treated K562 cells with CCA-1.1 and PGV-1 alone or in combination to determine the half-maximal concentration growth-inhibitory concentration and combination index score. The two compounds shared similar predicted target genes in mitosis, and CCA-1.1 mainly targeted Aurora A kinase in K562 cells with relatively low docking scores against the inhibitor in molecular docking analysis. Both compounds exhibited a similar inhibitory influence, and their co-treatment resulted in a synergistic effect on K562 cells. In conclusion, we indicated that CCA-1.1 and PGV-1 possibly target mitosis in cell cycle progression and, along with their specific targets, exhibit their synergistic activity in CML. These findings should be validated through experimental studies to provide data on the pharmacological activities of CCA-1.1 for CML treatment.