Inhibition of tumor growth in vitro and in vivo by fucoxanthin against human leukemia HL-60 cells and melanoma B16F10 cells

Abstract

In 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. These results suggest 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. 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. These results suggest 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.