Abstract
Fucoidan is an active component of seaweed, which inhibits proliferation and induces apoptosis of several tumor cells while the detailed mechanisms underlying this process are still not clear. In this study, the effect of Fucoidan on the proliferation and apoptosis of human breast cancer MCF-7 cells and the molecular mechanism of Fucoidan action were investigated. Viable cell number of MCF-7 cells was decreased by Fucoidan treatment in a dose-dependent manner as measured by MTT assay. Fucoidan treatment resulted in G1 phase arrest of MCF-7 cells as revealed by flow cytometry, which was associated with the decrease in the gene expression of cyclin D1 and CDK-4. Annexin V/PI staining results showed that the number of apoptotic cells was associated with regulation of cytochrome C, caspase-8, Bax and Bcl-2 at transcriptional and translational levels. Both morphologic observation and Hoechst 33258 assay results confirmed the pro-apoptotic effect of Fucoidan. Meanwhile, the ROS production was also increased by Fucoidan treatment, which suggested that Fucoidan induced oxidative damage in MCF-7 cells. The results of present study demonstrated that Fucoidan could induce G1 phase arrest and apoptosis in MCF-7 cells through regulating the cell cycle and apoptosis-related genes or proteins expression, and ROS generation is also involved in these processes.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Antineoplastic Agents / chemistry
- Antineoplastic Agents / pharmacology
- Apoptosis / drug effects*
- Apoptosis / genetics
- Blotting, Western
- Breast Neoplasms / genetics
- Breast Neoplasms / metabolism
- Breast Neoplasms / pathology
- Caspase 8 / genetics
- Caspase 8 / metabolism
- Caspases / genetics
- Caspases / metabolism*
- Cell Proliferation / drug effects
- Cell Size / drug effects
- Cyclin D1 / genetics
- Cyclin D1 / metabolism
- Cyclin-Dependent Kinase 4 / genetics
- Cyclin-Dependent Kinase 4 / metabolism
- Cytochromes c / genetics
- Cytochromes c / metabolism
- Dose-Response Relationship, Drug
- Fucus / chemistry
- G1 Phase Cell Cycle Checkpoints / drug effects*
- G1 Phase Cell Cycle Checkpoints / genetics
- Gene Expression Regulation, Neoplastic / drug effects
- Humans
- MCF-7 Cells
- Microscopy, Fluorescence
- Molecular Structure
- Polysaccharides / chemistry
- Polysaccharides / pharmacology*
- Proto-Oncogene Proteins c-bcl-2 / genetics
- Proto-Oncogene Proteins c-bcl-2 / metabolism
- Reactive Oxygen Species / metabolism*
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction / drug effects
- bcl-2-Associated X Protein / genetics
- bcl-2-Associated X Protein / metabolism
Substances
- Antineoplastic Agents
- Polysaccharides
- Proto-Oncogene Proteins c-bcl-2
- Reactive Oxygen Species
- bcl-2-Associated X Protein
- Cyclin D1
- Cytochromes c
- fucoidan
- CDK4 protein, human
- Cyclin-Dependent Kinase 4
- Caspase 8
- Caspases