title: Inhibition of proliferation of a hepatoma cell line by fucoxanthin in relation to cell cycle arrest and enhanced gap junctional intercellular communication.
abstract: 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 (1-20microM) strongly and concentration-dependently inhibited the proliferation of SK-Hep-1 cells at 24h of incubation, whereas fucoxanthin facilitated the growth of a murine embryonic hepatic (BNL CL.2) cells at 24h of incubation and only slightly slowed the cell proliferation at 48h. 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.
authors.affiliation: Department of Food Science, National Chung-Hsing University, 250 Kuo-Kuang Road, Taichung, 402, Taiwan.
authors.forename: Cheng-Ling
authors.initials: CL
authors.lastname: Liu
authors.forename: Yung-Sheng
authors.initials: YS
authors.lastname: Huang
authors.forename: Masashi
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Miyashita
authors.forename: Miao-Lin
authors.initials: ML
authors.lastname: Hu
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002450:Cell Communication / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy*; D051189:Murinae; D012333:RNA, Messenger / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D024341:Xanthophylls / Q000494:pharmacology* / Q000627:therapeutic use; D000097002:Gap Junction beta-1 Protein
chemical_list: D016588:Anticarcinogenic Agents; D002118:Calcium; D018031:Connexin 43; D017630:Connexins; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D012333:RNA, Messenger; D024341:Xanthophylls; D000097002:Gap Junction beta-1 Protein; C025164:fucoxanthin