Cytotoxic, Antioxidant, and Anti-Genotoxic Properties of Combretastatin A4 in Human Peripheral Blood Mononuclear Cells: A Comprehensive In Vitro Study

Abstract

Despite significant advances in drug discovery and the promising antitumor potential of combretastatin A4 (CA-4), which selectively targets rapidly dividing cancer cells, CA-4’s effects on non-dividing human cells, such as peripheral blood mononuclear cells (PBMCs), remain unclear. The aim of this study is to evaluate the in vitro bioactivity of CA-4 in human PBMCs, focusing on its antigenotoxic and antioxidant properties, while comparing its cytotoxic potency against PBMCs, cancer cell lines (JAR and HeLa), and the normal trophoblast cell line HTR-8/SVneo. Cell viability and metabolic activity were evaluated using the MTT assay. ROS production in PBMCs was measured using the H2DCFDA assay, and DNA damage was assessed using the Comet assay. CA-4 showed cytotoxicity in PBMCs and HTR-8/SVneo cells at concentrations above 200 µM, while cancer cells, JAR and HeLa, showed cytotoxicity at 100 µM and 1 µM, respectively. CA-4 also reduced ROS levels in PBMCs under oxidative stress and showed antioxidant effects at concentrations from 1 to 200 µM. In addition, CA-4 showed antigenotoxic effects against H2O2-induced DNA damage in PBMCs at concentrations of up to 1 µM. CA-4 exhibited lower cytotoxicity in human PBMCs compared to cancer cells, inhibited ROS production, and showed antioxidant and antigenotoxic properties, providing insight into its potential therapeutic efficacy and safety.