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Selective inhibition of cell proliferation and DNA synthesis by the polysulphated carbohydrate l-carrageenan
- Source :
- Cancer chemotherapy and pharmacology. 36(4)
- Publication Year :
- 1995
-
Abstract
- l-Carrageenan is a polysulphated carbohydrate that antagonises some heparin-binding growth factors. We assessed the effect of l-carrageenan on the proliferation of a panel of cell lines, some of which require heparin-binding growth factors for mitogenesis. The importance of growth factor antagonism for the anti-proliferative activity was also determined. Cell proliferation was determined by cell counts and a tetrazolium dye (MTT) assay, and DNA synthesis was determined by thymidine incorporation. The proliferation of the basic fibroblast growth factor (bFGF)-dependent endothelial cell line FBHE was inhibited by daily administration of l-carrageenan in a dose-dependent manner [concentration inhibiting cell growth by 50% (IC50 value), approx. 0.5 microgram/ml]. However, excess bFGF did not reverse the inhibitory effect. DNA synthesis was completely inhibited by concentrations of l-carrageenan that nonetheless allowed significant protein synthesis to occur. The proliferation of the androgen-dependent prostate-carcinoma cell line LNCaP was also inhibited by l-carrageenan (IC50 value, 5.5 micrograms/ml) and the cells were arrested at the G1/S boundary. l-Carrageenan inhibited DNA synthesis in MCF-7 cells stimulated by bFGF and transforming growth factor alpha (TGF alpha) but not in those stimulated by insulin-like growth factor 1 (IGF-1). Blocking IGF-1-mediated DNA synthesis with anti-IGF-1 receptor antibody alpha IR3 enhanced the inhibitory activity of l-carrageenan against MCF-7 cells grown in serum. A number of other transformed and non-transformed cell lines were either partially inhibited or not inhibited by l-carrageenan. l-Carrageenan had low anti-coagulant activity. l-Carrageenan is a selective anti-proliferative agent and warrants further investigation for anti-angiogenic therapy (in view of its activity against endothelial cells) and for the treatment of androgen-dependent prostate cancer.
- Subjects :
- Male
Cancer Research
TGF alpha
Angiogenesis
medicine.medical_treatment
Basic fibroblast growth factor
Antineoplastic Agents
Breast Neoplasms
Biology
Toxicology
Carrageenan
chemistry.chemical_compound
medicine
Tumor Cells, Cultured
Humans
Pharmacology (medical)
Endothelium
Cells, Cultured
Pharmacology
DNA synthesis
Cell growth
Growth factor
Prostatic Neoplasms
DNA
DNA, Neoplasm
Molecular biology
Growth Inhibitors
Endothelial stem cell
Oncology
chemistry
Biochemistry
Cell culture
Depression, Chemical
Female
Fibroblast Growth Factor 2
Cell Division
Subjects
Details
- ISSN :
- 03445704
- Volume :
- 36
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cancer chemotherapy and pharmacology
- Accession number :
- edsair.doi.dedup.....8d6e71ee2c41b152def48a4012dcab85