Anti-Angiogenesis of Theaflavin-Derived Copper Oxide: Comparative Analysis of In Vitro and In Vivo Models

Abstract

Angiogenesis is almost always paired with tumor progression and metastasis, therefore attended to with utmost importance by anticancer strategists. This study is therefore concerned with the green synthesis of a nanomaterial drug of anticancer interest: copper oxide nanoparticles synthesized with theaflavin, where theaflavin acts as a natural reducing and stabilizing agent. After characterization studies, the particles were found to have a size in the 40-70 nm range, double spherical morphology, and crystalline nature (as evidenced by PXRD), with absorption maxima at 290 nm in UV-Visible spectroscopy. In vitro studies conducted on lung cancer cells, A549, showed cytotoxicity in a dose-dependent manner, with cell viability going down sharply at 50 and 100 µg/mL; synchronous with these, were the enhanced production of reactive oxygen species, with an apex at 50 µg/mL. CAM inhibition of neovascularization was observed including reduced branching vessels, density of vessels, and complexity of vessels after treatment with CuO-TF. This is shown by the downregulation of proangiogenic markers VEGFA, VEGFR2, HIF1A, and ANGPTL4 and upregulation of the antiangiogenic marker THBS1, signifying that angiogenic signaling is going on to be suppressed at the transcriptional level.