Using UV–Vis Titration to Elucidate Novel EGCG-Induced Stabilization of the c-MYC G-Quadruplex

The c-MYC oncogene is frequently overexpressed in various human cancers, including aggressive brain tumors like glioblastoma, contributing significantly to tumor cell proliferation and survival. The promoter region of c-MYC contains guanine-rich sequences capable of forming non-canonical DNA structures known as G-quadruplexes (G4s). Stabilization of these G4 structures by small molecule ligands represents a potential therapeutic strategy to downregulate c-MYC expression. Polyphenols, naturally occurring compounds found in plants, possess diverse biological activities, including anticancer effects, and some have been implicated in DNA interactions. Here, we investigate the direct interaction between Epigallocatechin gallate (EGCG), a major polyphenol in green tea, and a synthetic oligonucleotide sequence (Pu27) known to form the predominant G4 structure in the c-MYC promoter. Using simple UV-Vis absorbance spectroscopy, we performed titration experiments by adding increasing concentrations of EGCG to a fixed concentration of pre-formed c-MYC G4 DNA in a potassium-containing buffer. We observed distinct spectral changes upon EGCG addition, notably a concentration-dependent hyperchromicity at the DNA absorbance maximum (~260 nm) and concurrent changes, including hypochromicity and a slight red-shift, near the EGCG absorbance maximum (~275 nm). These spectral perturbations are indicative of a direct interaction between EGCG and the c-MYC G4 DNA structure in vitro. While preliminary, these findings support the hypothesis that EGCG can bind to c-MYC G4 DNA and warrant further investigation into the nature and potential biological significance of this interaction.