ROS-Dependent Antiproliferative Effect of Brassinin Derivative Homobrassinin in Human Colorectal Cancer Caco2 Cells

摘要: This study was designed to examine the in vitro antiproliferative effect of brassinin and its derivatives on human cancer cell lines. Among seven tested compounds, homobrassinin (K1; N-[2-(indol-3-yl)ethyl]-S-methyldithiocarbamate) exhibited most potent activity with IC50 = 8.0 μM colorectal Caco2 cells selected for further studies. The flow cytometric analysis revealed a K1-induced increase G2/M phase associated dysregulation α-tubulin, α1-tubulin β5-tubulin expression. These findings suggest that inhibitory K1 can be mediated via inhibition microtubule formation. Furthermore, simultaneously arrest, also increased population sub-G1 DNA content which is considered marker apoptotic death. Apoptosis confirmed by annexin V/PI double staining, fragmentation assay chromatin condensation assay. apoptosis loss mitochondrial membrane potential (MMP), caspase-3 activation as well intracellular reactive oxygen species (ROS) production. Moreover, antioxidant Trolox blocked ROS production, changes MMP decreased cytotoxicity, important role apoptosis. Taken together, our data demonstrate induces ROS-dependent provide rationale vivo anticancer investigation.