Fucoxanthin induces apoptosis in human leukemia HL-60 cells through a ROS-mediated Bcl-xL pathway.

Abstract

Fucoxanthin, a natural biologically active substance isolated from Ishige okamurae, evidences antitumor activity in human leukemia cell HL-60 cells via the induction of apoptosis. However, the mechanism underlying fucoxanthin-induced apoptosis in HL-60 cells remains unclear. In this study, we focused on the effect of fucoxanthin induction on the accumulation of reactive oxygen species (ROS), and on the triggering of Bcl-xL signaling pathway in HL-60 cells. We determined that ROS are generated during fucoxanthin-induced cytotoxicity and apoptosis in HL-60 cells, and that N-acetylcysteine (NAC), a ROS scavenger, suppressed fucoxanthin-induced cytotoxicity and apoptosis. Moreover, fucoxanthin-induced the cleavage of caspases -3 and -7, and poly-ADP-ribose polymerase (PARP) and a decrease of Bcl-xL levels, whereas NAC pre-treatment significantly inhibited caspase-3, -7, and PARP cleavage and the reduction in Bcl-xL levels. In this study, it was demonstrated for the first time that fucoxanthin generated ROS and that the accumulation of ROS performed a crucial role in the fucoxanthin-induced Bcl-xL signaling pathway.

• Authors: Kil-Nam Kim, Soo-Jin Heo, Sung-Myung Kang, Ginnae Ahn, You-Jin Jeon
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 24 Issue 6 Pg. 1648-54 (Sep 2010) ISSN: 1879-3177 [Electronic] England
• PMID: 20594983 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• BCL2L1 protein, human
• Caspase Inhibitors
• Free Radical Scavengers
• Plant Extracts
• Reactive Oxygen Species
• Xanthophylls
• bcl-X Protein
• fucoxanthin
• PARP1 protein, human
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases
• Caspases
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Caspase Inhibitors
• Caspases (metabolism)
• Cell Cycle (drug effects)
• Cell Nucleus (drug effects, metabolism)
• Cell Survival (drug effects)
• Drug Antagonism
• Free Radical Scavengers (pharmacology)
• HL-60 Cells
• Humans
• Leukemia (drug therapy, metabolism, pathology)
• Phaeophyceae (chemistry)
• Plant Extracts (chemistry, pharmacology)
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Xanthophylls (pharmacology)
• bcl-X Protein (metabolism)