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

Despite significant progress in drug discovery and the promising antitumor potential of Combretastatin-A4 (CA-4) in selectively targeting rapidly dividing cancer cells, its effects on non-dividing human cells, such as peripheral blood mononuclear cells (PBMCs), remain unclear. This study aims to assess the in vitro bioactivity of CA-4 in human PBMCs, with a focus 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 was assessed using MTT assay. ROS production in PBMCs was measured by H2DCFDA assay, and DNA damage was evaluated through comet assay. CA-4 exhibited cytotoxicity in PBMCs and HTR-8/SVneo cells at concentrations above 200 µM, while cancer cells, JAR and HeLa, demonstrated cytotoxicity at 100 µM and 1 µM, respectively. CA-4 also reduced ROS levels in PBMCs under oxidative stress, showing antioxidant effects across concentrations ranging from 1 to 200 µM. Additionally, CA-4 demonstrated antigenotoxic effects against H2O2-induced DNA damage in PBMCs at concentrations up to 1 µM. CA-4 exhibited lower cytotoxicity in human PBMCs compared to cancer cells, inhibited ROS production, and demonstrated antioxidant and antigenotoxic properties, offering insights into its potential therapeutic efficacy and safety.