COX-2 downregulation via G-quadruplex structure induction in the PTGS2-promoter region by mononuclear octahedral cobalt(III) Schiff base complex [CoL] in colorectal cancer cells.

G-quadruplex structures within the promoter regions of some oncogenes diminish transcriptional activity. The suppression and downregulation of Cyclooxygenase-2 (COX-2), which is encoded by the prostaglandin-endoperoxide synthase 2 (PTGS2) gene, could control the size of colorectal cancer tumors. This study aimed to investigate the impact of a mononuclear octahedral cobalt(III) Schiff base complex [CoL] (L = 2-((allylimino)methyl)-6-methoxyphenol) on the G-quadruplex structures in the PTGS2 promoter region and to assess its downregulation effects in the human colorectal cancer cell line HT-29. At first, molecular docking was used to evaluate the binding of [CoL] to the PTGS2 promoter region. Then, the potential and stabilization of G-quadruplex formation in the PTGS2 promoter motifs were investigated using circular dichroism (CD) spectroscopy, polyacrylamide gel electrophoresis, and polymerase chain reaction (PCR) stop assays. COX-2 expression was also assessed by real-time PCR and western blot. Molecular docking analysis indicates that [CoL] has a potent interaction with the PTGS2 promoter region. Additionally, [CoL] has an intense inhibitory effect on the PTGS2-PCR stop assay. The CD measurements confirmed the conformational property of G-quadruplex DNA structures induced by [CoL]. Treatment of colorectal cancer cells with the [CoL] resulted in a modest increase in PTGS2 expression by a mean factor of 1.69 (p < 0.05). Conversely, the expression of COX-2 proteins was downregulated significantly, with a mean protein intensity of 0.47 (p < 0.001). Therefore, [CoL] induces G-quadruplex formation in the promoter region of PTGS2, which ultimately inhibits protein expression of COX-2. This means that [CoL] can be an effective agent for colorectal cancer treatment.