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

Numerous studies demonstrated CCA-1.1, the modified compound from PGV-1, inhibits tumor cells growth in breast and colorectal cancer. This time, we used bioinformatics and molecular interaction approaches to ascertain the potential CCA-1.1 activity target focusing on leukemia, along with the cytotoxic test in leukemia cells. Genomics data expression was collected through the COSMIC database by selecting 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 between the 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 the cell cycle and mitosis collected through GeneCards. A molecular docking study was applied to determine the molecular interaction between CCA-1.1 or PGV-1 and the predicted protein target. We carried out a cytotoxic test using a trypan blue exclusion assay. We treated K562 cells with CCA-1.1 and PGV-1 in single and combination treatment to determine the half concentration of growth inhibitory (GI50) and combination index (CI) score. CCA-1.1 and PGV-1 shared similar predicted target genes in mitosis, and interestingly CCA-1.1 were mainly targeted in Aurora A (AURKA) in K562 cells with lower docking scores against the inhibitor in molecular docking analysis. Moreover, each compound exhibited an inhibitory effect similarly, and the co-treatment resulted in a synergistic effect in K562 cells. Collectively, we indicated that CCA-1.1 and PGV-1 possibly targeted mitosis in cell cycle progression, and along with their specific targets, led to their synergistic activity in CML. These findings should be validated through experimental studies to provide more pharmacological activities of CCA-1.1 to cure CML.