title: 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 p16(INK4a)-Rb and p14(Arf)-p53 pathways. Furthermore, upregulation of p16(INK4a) 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 p14(Arf) expression as cells enter quiescence, with the reduction of p16(INK4a). 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.
authors.affiliation: Institute of Fisheries Sciences, Pukyong National University, Ilgwang-ro, Ilgwang-myeon, Gijang-gun, Busan 619-911, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Min
authors.affiliation: Institute of Fisheries Sciences, Pukyong National University, Ilgwang-ro, Ilgwang-myeon, Gijang-gun, Busan 619-911, Republic of Korea.
authors.forename: In-Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Institute of Fisheries Sciences, Pukyong National University, Ilgwang-ro, Ilgwang-myeon, Gijang-gun, Busan 619-911, Republic of Korea.
authors.forename: Jungim
authors.initials: J
authors.lastname: Lee
authors.affiliation: Institute of Fisheries Sciences, Pukyong National University, Ilgwang-ro, Ilgwang-myeon, Gijang-gun, Busan 619-911, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Institute of Fisheries Sciences, Pukyong National University, Ilgwang-ro, Ilgwang-myeon, Gijang-gun, Busan 619-911, Republic of Korea.
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Institute of Fisheries Sciences, Pukyong National University, Ilgwang-ro, Ilgwang-myeon, Gijang-gun, Busan 619-911, Republic of Korea.
authors.forename: Taek-Jeong
authors.initials: TJ
authors.lastname: Nam
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D011134:Polysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011134:Polysaccharides; D016160:Retinoblastoma Protein; C007789:fucoidan