RELEVANT CYTOTOXIC ACTIVITY OF A NOVEL PEGYLATED CHRYSIN ON HUMAN HEPATOMA CELL LINE (HEPG2)

GASSER FB; OGGERO, JULIA; BELTRAMINO MF; ENGLER C; SIMONETTO C; BARAVALLE M.E; ORTEGA H.H.; VAILLARD, S; VAILLARD, V

Mar del Plata

Congreso; LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2023

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)

Chrysin is a natural flavonoid found in honey and plants which has several biological properties such as antioxidant, anti-inflammatory and antitumoral capacity. PEGylation of hydrophobic drugs improves their aqueous solubility, cellular uptake and overall therapeutic efficacy. In this study, we investigated the effect of a novel PEGylated chrysin (CP), achieved by substitution reaction, on in vitro cytotoxicity, reactive oxygen species (ROS) and Lactate dehydrogenase (LDH) production, genotoxic activity and cell migration in human hepatoma cells (HepG2). The cytotoxic activity of CP was evaluated after exposure with increasing concentrations (10-200ug/ml) and Paclitaxel (PTX) as positive control for 48h through the MTT assay. The leakage of LDH into the medium as an indicator of cell membrane damage was detected with an LDH kit (Wiener Lab) and triton X-100 was used as positive control. Intracellular production of ROS was evaluated using staining with dihydroethidium and analyzed by flow cytometry. The genotoxic activity of CP was evaluated using micronucleus assay and cell migration evaluation was carried out using the in vitro scratch wound-healing assay. A dose-dependent decreasing cell viability curve and increasing LDH production was obtained in HepG2 cells. The IC50 value obtained for CP was 55 µg/ml. Treatment with CP at concentration of IC50 and IC50/2 values produces dose-dependent ROS compared to untreated cells (p