Fucoxanthin suppresses tumor growth of human leukemia HL-60 cells and melanoma B16F10 cells in vitro and in vivo

Abstract

The purpose of the present study, we designed to evaluate the molecular mechanism of fucoxanthin isolated from brown algae against HL-60 and B16F10 cell lines. We found that ROS are generated during fucoxanthin-induced apoptosis in HL-60 cells, and NAC which is a scavenger of ROS, suppressed fucoxantin-induced cytotoxicity and apoptosis. Furthermore, the treatment with NAC dramatically inhibited fucoxanthin-induced phosphorylation of JNK and p38 kinase in HL-60 cells. Moreover, fucoxanthin reduced the viability of B16F10 cells in a dose-dependent manner accompanied by the induction of cell cycle arrest during the G0/G1 phase and apoptosis. Fucoxanthin-induced G0/G1 arrest was associated with a marked decrease in the protein expressions of phosphorylated-Rb, cyclin D and Cdk4 and up-regulation of the protein levels of p15INK4B and p27Kip1. Fucoxanthin-induced apoptosis was accompanied with down-regulation of the protein levels of Bcl-xL, and inhibitor of apoptosis protein, resulting in cytochrome c release and sequential activation of caspase-9, caspase-3, and PARP. Furthermore, fucoxanthin activated JNK, MAPK and ERK on B16F10 cells. This study suggested that fucoxanthin has anti-tumor effects on HL-60 and B16F10 cell lines by inducing selectively the genes related to apoptosis which provided further theoretical support for the application of fucoxanthin as a promising anti-tumor agent.lls, and NAC which is a scavenger of ROS, suppressed fucoxantin-induced cytotoxicity and apoptosis. Furthermore, the treatment with NAC dramatically inhibited fucoxanthin-induced phosphorylation of JNK and p38 kinase in HL-60 cells. Moreover, fucoxanthin reduced the viability of B16F10 cells in a dose-dependent manner accompanied by the induction of cell cycle arrest during the G0/G1 phase and apoptosis. Fucoxanthin-induced G0/G1 arrest was associated with a marked decrease in the protein expressions of phosphorylated-Rb, cyclin D and Cdk4 and up-regulation of the protein levels of p15INK4B and p27Kip1. Fucoxanthin-induced apoptosis was accompanied with down-regulation of the protein levels of Bcl-xL, and inhibitor of apoptosis protein, resulting in cytochrome c release and sequential activation of caspase-9, caspase-3, and PARP. Furthermore, fucoxanthin activated JNK, MAPK and ERK on B16F10 cells. This study suggested that fucoxanthin has anti-tumor effects on HL-60 and B16F10 cell lines by inducing selectively the genes related to apoptosis which provided further theoretical support for the application of fucoxanthin as a promising anti-tumor agent.