Fucoxanthin induces G0/G1 phase arrest and apoptosis in melanoma B16F10 cells through Akt and Bcl-xL signaling pathway

Abstract

The present study was designed to evaluate the molecular mechanisms of fucoxanthin against melanoma cell lines (B16F10 cells). 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 (retinoblastoma protein), cyclin D (1 and 2) and cyclin-dependent kinase (Cdk)4 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 (XIAP), resulting in cytochrome c release and sequential activation of caspase-9, caspase-3, and PARP. Furthermore, fucoxanthin activated c-Jun N-terminal kinase (JNK), p38 MAPK (p38) and extracellular signal-regulated kinase (ERK) on B16F10 cells in a time-dependent manner. These results suggest that fucoxanthin has anti-tumor properties on melanoma cells by inducing selectively the genes related to cell cycle arrest and apoptosis.