The effects of fucodian on senescence are controlled by the p16INK4a-pRb and p14Arf-p53 pathways in hepatocellular carcinoma and hepatic cell lines.

Abstract

Fucoidan is known to have various pharmacological effects, including antitumor activity. Although it has potential as a therapeutic agent for cancer cells, the anti-senescence effects and detailed mechanism of action remain poorly understood in normal hepatic cells. We investigated the anticancer functions of fucoidan using HepG2 cells as well as the mechanisms mediating the anti-senescent actions in Chang liver cells. Fucoidan effectively inhibited HepG2 cell viability and induced apoptosis. Also, fucoidan-induced G1 phase arrest was caused by the activity of the p16INK4a-Rb and p14Arf-p53 pathways. Furthermore, upregulation of p16INK4a was critical to the antitumor activity of HepG2 cells treated with fucoidan and was correlated with inhibition of Cdk4 and pRb and upregulation of p21 expression. Our results suggest that fucoidan upregulates INK4a locus genes to induce apoptosis through p38 MAPK in HepG2 cells. Moreover, it prevents cellular senescence of Chang-L cells, by decreasing p14Arf expression as cells enter quiescence, with the reduction of p16INK4a. Fucoidan treatment also downregulated the expression of α2M. In conclusion, fucoidan can be considered a potential therapeutic agent against liver cancer that does not cause senescence in normal hepatic cells. Thus, it may be possible to use fucoidan therapeutically in both tumor suppression and aging.