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

Toxicol In Vitro. 2010 Sep;24(6):1648-54. doi: 10.1016/j.tiv.2010.05.023. Epub 2010 Jun 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Drug Antagonism
  • Free Radical Scavengers / pharmacology
  • HL-60 Cells
  • Humans
  • Leukemia / drug therapy*
  • Leukemia / metabolism
  • Leukemia / pathology
  • Phaeophyta / chemistry*
  • Plant Extracts / chemistry
  • Plant Extracts / 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

Substances

  • 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