λ-Carrageenan oligosaccharides elicit reactive oxygen species production resulting in mitochondrial-dependent apoptosis in human umbilical vein endothelial cells

Previous studies have shown that highly sulfated lambda-carrageenan oligosaccharides (lambda-CO) possess all anti-angiogenetic effect, while high concentrations of lambda-CO present a cytotoxic effect towards human umbilical vein endothelial cells (HUVECs). The aim of this Study was to explore the underlying mechanism of lambda-CO on inhibiting cell proliferation. lambda-CO elicited reactive oxygen species (ROS) production with concentrations at 0.8 and 1 mg/ml, and this event was accompanied by the increase of early apoptotic cells, nuclear morphology changes and cell cycle arrest at the S and G(2)/M phases. However, prevention of oxidative stress by N-acetyl-L-cysteine (NAC) could abolish the effect of lambda-CO on these events. Yet, lambda-CO induced a depolarization of mitochondrial transmembrane potential. At 0.8 mg/ml, lambda-CO induced up-regulation of p53 and Bax, down-regulation of Bcl-2 and activation of caspase-9 and -3. These results suggest that exposure to a high concentration of lambda-CO activates the mitochondrial-mediated apoptotic pathway and cell cycle arrest by generation of ROS.