Concomitant induction of apoptosis and suppression of epithelial-mesenchymal transition (EMT) by a Cu(II)-flavonoid complex in colorectal cancer.

Notwithstanding progress in chemotherapy, cancer recurrence resulting from metastasis continues to be a significant challenge. Consequently, targeting the epithelial-mesenchymal transition (EMT) has emerged as a viable approach to impede metastasis and enhance therapy success. In colorectal cancer, current initiatives focus on discovering new agents that are both efficacious and less harmful to normal cells. Plant-derived flavonoids and metal-based compounds exhibit significant medicinal potential. This research examined the anticancer efficacy of a Cu(II)-flavonoid complex comprising quercetin and 1,10-phenanthroline ligands in colorectal cancer cell lines HCT-116 and HT-29. The sulforhodamine B (SRB) assay assessed cell viability, yielding IC₅₀ values of 3.19 μM for HCT-116 and 1.81 μM for HT-29 after 48 h, but the individual ligands demonstrated no similar cytotoxicity. The compound exhibited lower cytotoxicity to normal colon cells (CCD-18Co) than toward colorectal cancer cells (HCT-116 and HT-29). Apoptosis induction was verified with Hoechst 33342, Annexin-V-FITC, and propidium Iodide staining, supplemented by M30-antigen ELISA, and further corroborated by the pan-caspase inhibitor Z-VAD-FMK and elevated levels of apoptotic protein markers such as cleaved caspase-8 and parp-1. Flow cytometry revealed G₀/G₁ phase arrest, indicating caspase-dependent apoptotic cell death. The compound also impeded epithelial-mesenchymal transition, as demonstrated by a dose-dependent reduction in migration and invasion in wound healing and Matrigel invasion experiments. Western blot analysis revealed elevated levels of E-cadherin and reduced levels of N-cadherin, vimentin, and snail. The Cu(II)-flavonoid combination demonstrates significant anti-proliferative, pro-apoptotic, and anti-metastatic properties in colorectal cancer cells, while exhibiting lower cytotoxic effects in normal colon cells. This underscores its potential as a viable candidate for additional molecular and in vivo assessment of the complex in colorectal cancer.