λ-Carrageenan oligosaccharides elicit reactive oxygen species production resulting in mitochondrial-dependent apoptosis in human umbilical vein endothelial cells
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- Published online on: December 1, 2009 https://doi.org/10.3892/ijmm_00000295
- Pages: 801-806
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Abstract
Previous studies have shown that highly sulfated λ-carrageenan oligosaccharides (λ-CO) possess an anti-angiogenetic effect, while high concentrations of λ-CO present a cytotoxic effect towards human umbilical vein endothelial cells (HUVECs). The aim of this study was to explore the underlying mechanism of λ-CO on inhibiting cell proliferation. λ-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 G2/M phases. However, prevention of oxidative stress by N-acetyl-L-cysteine (NAC) could abolish the effect of λ-CO on these events. Yet, λ-CO induced a depolarization of mitochondrial transmembrane potential. At 0.8 mg/ml, λ-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 λ-CO activates the mitochondrial-mediated apoptotic pathway and cell cycle arrest by generation of ROS.