Lambda-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 an 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 G2/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.
Chen
Hai-Min
HM
Ningbo University, Key Laboratory of Applied Marine Biotechnology, Ministry of Education, Zhejiang 315211, PR China.
Yan
Xiao-Jun
XJ
Mai
Ting-Yan
TY
Wang
Feng
F
Xu
Wei-Feng
WF
D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002351:Carrageenan / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014471:Umbilical Veins; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D002351:Carrageenan; D053148:Caspase 3; D053453:Caspase 9; D000111:Acetylcysteine