PEGylated Chrysin: In Vitro Biological Activity and Mechanistic Insights in HepG2 Cells
Fátima Belén Gasser, Julia Oggero, María Sol Renna, María Florencia Beltramino, Candela Simonetto, Lucía Dominguez, Hugo Héctor Ortega, Santiago Eduardo Vaillard, Victoria Anahí Vaillard, María Eugenia BaravalleABSTRACT
PEGylated chrysin, a natural flavonoid conjugated with methoxypolyethylene glycol, exhibits in vitro cytotoxic properties, likely through apoptosis induction. In this study, we investigated its biological effects on HepG2 hepatocellular carcinoma cells, comparing its activity with the chemotherapeutic agent paclitaxel. We evaluated reactive oxygen species (ROS) production, membrane integrity, DNA damage, and wound closure using the scratch assay. At equivalent concentrations, PEGylated chrysin induced higher cell membrane damage but generated lower ROS levels compared to paclitaxel. Both compounds exhibited similar efficacy to reduce wound closure under the evaluated experimental conditions. Additionally, PEGylated chrysin significantly increased the frequency of micronuclei in binucleated cells, indicating genotoxic potential. To assess cellular uptake, a novel fluorescein−tagged conjugate (fluorescein−PEG−chrysin) was synthesized which demonstrated that the PEGylated drug is accumulated in the cytoplasm of HepG2 cells. These results highlight PEGylated chrysin as a promising candidate with antiproliferative potential, capable of inducing diverse cellular damage pathways in liver cancer cells while showing a distinct cytotoxic profile compared with Paclitaxel.