Abstract
Fucoidan, a fucose-rich polysaccharide isolated from brown alga, is currently under investigation as a new anti-cancer compound. In the present study, fucoidan extract (FE) from Cladosiphon navae-caledoniae Kylin was prepared by enzymatic digestion. We investigated whether a combination of FE with cisplatin, tamoxifen or paclitaxel had the potential to improve the therapeutic efficacy of cancer treatment. These co-treatments significantly induced cell growth inhibition, apoptosis, as well as cell cycle modifications in MDA-MB-231 and MCF-7 cells. FE enhanced apoptosis in cancer cells that responded to treatment with three chemotherapeutic drugs with downregulation of the anti-apoptotic proteins Bcl-xL and Mcl-1. The combination treatments led to an obvious decrease in the phosphorylation of ERK and Akt in MDA-MB-231 cells, but increased the phosphorylation of ERK in MCF-7 cells. In addition, we observed that combination treatments enhanced intracellular ROS levels and reduced glutathione (GSH) levels in breast cancer cells, suggesting that induction of oxidative stress was an important event in the cell death induced by the combination treatments.
MeSH terms
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Antineoplastic Agents / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Apoptosis / drug effects
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Apoptosis / genetics
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Cell Cycle / drug effects
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Cell Cycle / genetics
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Cell Line, Tumor
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Cisplatin / administration & dosage
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Cisplatin / pharmacology
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Down-Regulation / drug effects
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Down-Regulation / genetics
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Drug Synergism
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Female
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Glutathione / genetics
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Glutathione / metabolism
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Humans
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / genetics
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MCF-7 Cells
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Myeloid Cell Leukemia Sequence 1 Protein
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Oxidative Stress / drug effects
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Oxidative Stress / genetics
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Paclitaxel / administration & dosage
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Paclitaxel / pharmacology
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Phaeophyceae / chemistry
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Phaeophyceae / metabolism
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Phosphorylation / drug effects
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Phosphorylation / genetics
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Plant Extracts / pharmacology*
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Polysaccharides / administration & dosage
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Polysaccharides / pharmacology*
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Reactive Oxygen Species / metabolism
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Tamoxifen / administration & dosage
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Tamoxifen / pharmacology
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bcl-X Protein / genetics
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bcl-X Protein / metabolism
Substances
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Antineoplastic Agents
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BCL2L1 protein, human
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Myeloid Cell Leukemia Sequence 1 Protein
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Plant Extracts
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Polysaccharides
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Proto-Oncogene Proteins c-bcl-2
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Reactive Oxygen Species
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bcl-X Protein
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Tamoxifen
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fucoidan
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Proto-Oncogene Proteins c-akt
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Glutathione
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Paclitaxel
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Cisplatin