Cell Cycle Arrest and Induction of Apoptosis in Colon Adenocarcinoma Cells by a DNA Intercalative Quinoline Derivative, 4-Morpholinopyrimido [4′,5′:4,5] Selenolo (2,3-b) Quinoline

Abstract

Circular dichroism, topological studies, molecular docking, absorbance, and fluorescence spectral titrations were employed to study the interaction of 4-morpholinopyrimido [4',5':4,5] selenolo (2,3-b) quinoline (MPSQ) with DNA. The association constants of MPSQ-DNA interactions were of the order of 10(4) M(-1). Melting temperature, topological, and docking studies confirmed that the mode of interaction was by intercalation with preference to d(GpC)-d(CpG) site of DNA. Cytotoxicity studies showed the MPSQ-induced dose-dependent inhibitory effect on the proliferation of different cancer cells. Colon adenocarcinoma (COLO 205) cells are more sensitive among the cell lines tested, with an IC50 value of 15 μM. Flow cytometry revealed that MPSQ affects the cell cycle progression by arresting at G2M phase. Further, Annexin V staining, mitochondrial membrane potential assay, and caspase-3 activity assay confirmed that MPSQ leads to mitochondria-mediated apoptotic cell death in COLO 205 cells.