Inhibition of proliferation of a hepatoma cell line by fucoxanthin in relation to cell cycle arrest and enhanced gap junctional intercellular communication

Fucoxanthin is one of the most abundant carotenoids found in Undaria pinnatifida and has been shown to inhibit tumor proliferation in vitro. However, the mechanisms underlying the anti-cancer effects of fucoxanthin are unclear. In this study, we hypothesized that fucoxanthin may cause cell cycle arrest and enhance gap junctional intercellular communication (GJIC) in SK-Hep-1 human hepatoma cells. Data revealed that fucoxanthin (1–20 μM) strongly and concentration-dependently inhibited the proliferation of SK-Hep-1 cells at 24 h of incubation, whereas fucoxanthin facilitated the growth of a murine embryonic hepatic (BNL CL.2) cells at 24 h of incubation and only slightly slowed the cell proliferation at 48 h. In SK-Hep-1 cells, fucoxanthin caused cell cycle arrest at G0/G1 phase and induced cell apoptosis, as evidenced by increased subG1 cells and induction of DNA strand breaks. Using scrape loading-dye-transfer assay, fucoxanthin was found to significantly enhance GJIC of SK-Hep-1 cells without affecting that of BNL CL.2 cells. In addition, fucoxanthin significantly increased protein and mRNA expressions of connexin 43 (Cx43) and connexin 32 (Cx32) in SK-Hep-1 cells. Moreover, fucoxanthin markedly increased the concentration of intracellular calcium levels in SK-Hep-1 cells. Thus, fucoxanthin is specifically antiproliferative against SK-Hep-1 cells, and the effect is associated with upregulation of Cx32 and Cx43, which enhances GJIC of SK-Hep-1 cells. The enhanced GJIC may be responsible for the increase of the intracellular calcium level, which then causes cell cycle arrest and apoptosis.