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

Abstract

Fucoxanthin, a natural biologically active substance isolated from Ishige okamurae, has potent antitumor activity of human leukemia cell HL-60 cells via apoptosis induction. However, the mechanism underlying fucoxanthin-induced apoptosis in HL-60 cells remains unclear. In the present study, we focused on the effect of fucoxanthin induction on reactive oxygen species (ROS) accumulation, and triggering the mitogen-activated protein kinase (MAPKs) signaling pathway in HL-60 cells. We found that ROS are generated during fucoxanthin-induced cytotoxicity and apoptosis in HL-60 cells, and N-acetylcysteine (NAC) which is a scavenger of ROS, suppressed fucoxanthin-induced cytotoxicity and apoptosis. Moreover, fucoxanthin dramatically increased phosphorylation of c-Jun N-terminal kinase (JNK) and p38 kinase when compared to the treatment without fucoxanthin but the treatment with NAC dramatically inhibited fucoxanthin-induced phosphorylation of JNK and p38 kinase in HL-60 cells. In addition, fucoxanthin-induced the cleavage of caspase-3, -7, and poly-ADP-ribose polymerase (PARP) and decrease of Bcl-xL levels, whereas NAC pre-treatment significantly inhibited the cleavage of caspase-3, -7, and PARP and decrease of Bcl-xL levels. In this study it was firstly demonstrated that fucoxanthin generated ROS and the accumulation of ROS played an important role in fucoxanthin-induced JNK/p38 MAPK signaling pathway, which provided further theoretical support for the application of fucoxanthin as a promising anticancer agent.