Fucoxanthin Induces Apoptosis in Human Leukemia HL-60 Cells Through a ROS-mediated Bcl-xL Pathway

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.