title: Growth inhibition of human hepatic carcinoma HepG2 cells by fucoxanthin is associated with down-regulation of cyclin D.
abstract: Fucoxanthin, a major carotenoid in brown sea algae, has recently been demonstrated by us to inhibit the proliferation of colon cancer cells, and this effect was associated with growth arrest. These results, taken together with previous studies with fucoxanthin, suggest that it may be useful in chemoprevention of other human malignancies. The present study was designed to evaluate the molecular mechanisms of fucoxanthin against hepatic cancer using the human hepatocarcinoma HepG2 cell line (HepG2). Fucoxanthin reduced the viability of HepG2 cells accompanied with the induction of cell cycle arrest during the G0/G1 phase at 25 microM. This concentration of fucoxanthin inhibited the phosphorylation of the retinoblastoma protein (Rb) at Serine 780 (Ser780) position 18 h after treatment. The kinase activity of cyclin D and cdk4 complex, responsible for the phosphorylation of Rb Ser780 site, was down-regulated 18 h after the treatment. Western blotting analysis revealed that the expression of cyclin D-type protein was suppressed by treatment of fucoxanthin. This reduction was partially blocked by concurrent treatment with the proteasome inhibitor MG132, indicating the involvement of the proteasome-mediated degradation. In addition, RT-PCR analysis revealed that fucoxanthin also appeared to repress cyclin D mRNA. Thus, both the protein degradation and transcriptional repression seem to be responsible for suppressed cyclin D level in fucoxanthin-treated HepG2 cells which may be related to the antitumorgenic activity.
authors.affiliation: Laboratory of Food and Nutritional Chemistry, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Kobe, Nada, Hyogo 657-8501, Japan.
authors.forename: Swadesh K
authors.initials: SK
authors.lastname: Das
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kanazawa
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D056741:Cyclin D; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D056743:Cyclin D3; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D016193:G1 Phase / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D024341:Xanthophylls / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C534696:CCND3 protein, human; D056741:Cyclin D; D056743:Cyclin D3; D016213:Cyclins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D024341:Xanthophylls; C025164:fucoxanthin; D019938:Cyclin D1