cyclin-d1 and fucoxanthin

Topics: Animals; Azoxymethane; Chemokines, CC; Colonic Neoplasms; Cyclin D1; Dextran Sulfate; Disease Models, Animal; Humans; Male; Mice; Mice, Inbred ICR; Proto-Oncogene Proteins c-akt; Receptors, CCR1; Smad2 Protein; Xanthophylls

Topics: Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cell Line, Tumor; Cyclin D1; Cyclooxygenase 2; Endometrial Neoplasms; Female; Humans; NF-kappa B; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; TOR Serine-Threonine Kinases; Xanthophylls

A xanthophyll of fucoxanthin (Fx) is a potential chemopreventive agent. Familial adenomatous polyposis (FAP) is an inherited disease that is associated with a high risk of developing colorectal cancer. However, it remains unclear whether Fx can modify colorectal tumorigenesis in Apc. We investigated the chemopreventive effect of Fx in dextran sodium sulfate (DSS)-treated Apc. Administration of Fx in the diet for 5 weeks significantly suppressed the number of colorectal adenocarcinomas in DSS-treated male Apc. Fx possesses chemopreventive potential against progression of colorectal carcinogenesis in Apc

Topics: Adenomatous Polyposis Coli; Animals; Anticarcinogenic Agents; Colorectal Neoplasms; Cyclin D1; Dextran Sulfate; Disease Models, Animal; Male; Mice; Xanthophylls

Fucoxanthin (FX) is a natural carotenoid with reported antitumorigenic activity. This study explored the effects of FX and its deacetylated product, fucoxanthinol (FXOH), on B-cell malignancies, including Burkitt's lymphoma, Hodgkin's lymphoma and Epstein-Barr virus-immortalized B cells. Both FX and FXOH reduced the viability of these malignant B cells in a dose-dependent manner accompanied by the induction of cell cycle arrest during G1 phase and caspase-dependent apoptosis. FXOH was approximately twice more potent than FX in these activities. In contrast, normal peripheral blood mononuclear cells were resistant to FX and FXOH. Strong and constitutive activation of nuclear factor-κB (NF-κB) is a common characteristic of many B-cell malignancies, and FXOH suppressed constitutive NF-κB activity. NF-κB inhibition was accompanied by downregulation of NF-κB-dependent anti-apoptotic and cell cycle regulator gene products, including Bcl-2, cIAP-2, XIAP, cyclin D1 and cyclin D2. The results indicated that FX and FXOH are potentially useful therapeutic agents in B-cell malignancies characterized by aberrant regulation of NF-κB.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; B-Lymphocytes; beta Carotene; Burkitt Lymphoma; Caspases; Cell Line, Transformed; Cyclin D1; Cyclin D2; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Herpesvirus 4, Human; Hodgkin Disease; Humans; NF-kappa B; X-Linked Inhibitor of Apoptosis Protein; Xanthophylls

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.

Topics: Blotting, Western; Carcinoma, Hepatocellular; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclin D; Cyclin D1; Cyclin D3; Cyclins; Dose-Response Relationship, Drug; Down-Regulation; G1 Phase; Gene Expression; Humans; Hydrolysis; Liver Neoplasms; Molecular Structure; Phosphorylation; Resting Phase, Cell Cycle; Retinoblastoma Protein; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Xanthophylls