Fucoidan extract enhances the anti-cancer activity of chemotherapeutic agents in breast cancer cells
© Shirahata et al.; licensee BioMed Central Ltd. 2013
Published: 4 December 2013
Fucoidan, a fucose-rich polysaccharide isolated from brown alga, is currently under investigation as a new anti-cancer compound [1–4]. 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 chemotherapeutic agents had the potential to improve the therapeutic efficacy of cancer treatment.
Materials and methods
Estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells were cultured in DME medium supplemented with 10% fetal bovine serum in a humidified atmosphere of 5% CO2 at 37 °C. The abalone glycosidase-digested fucoidan extract (FE) was obtained from Daiichi Sangyo Corporation (Osaka, Japan). The cells were treated with FE and chemotherapeutic agents like cisplatin, tamoxifen or paclitaxel. The cell growth was determined by MTT assay. Apoptosis was evaluated using annexin V binding assay and flow cytometry analysis. Signaling proteins were analyzed by western blot. Intracellular reactive oxygen species (ROS) were determined using DCFH-DA and determined using IN Cell Analyzer 1000. The reduced glutathione (GSH) concentration was measured by the GSH assay kit.
FE protected normal human fibroblast TIG-1 cells from apoptosis by cisplatin and tamoxifen, suggesting its favorable characteristic for application to cancer therapy.
Combination of FE and three chemotherapeutic agents exhibit highly synergistic inhibitory effects on the growth of breast cancer cells.
Combination treatments induced modifications in cell cycle distribution.
Combination treatments modified the Bcl-2 expression, and ERK and Akt phosphorylation induced by FE, demonstrating different effects on apoptotic pathways in MDA-MB-231 cells and MCF-7 cells.
Generation of intracellular ROS and depletion of GSH are related to the cell death in combination treated -breast cancer cells.
- Ye J, Li Y, Teruya K, Katakura Y, Ichikawa A, Eto H, Hosoi M, Hosoi M, Nishimoto S, Shirahata S: Enzyme-digested fucoidan extracts derived from seaweed Mozuku of Cladosiphon novae-caledoniae kylin inhibit invasion and angiogenesis of tumor cells. Cytotechnology. 2005, 47: 117-126. 10.1007/s10616-005-3761-8.PubMed CentralView ArticlePubMedGoogle Scholar
- Zhang Z, Teruya K, Eto H, Shirahata S: Fucoidan extract induces apoptosis in MCF-7 Cells via a mechanism involving the ROS-dependent JNK activation and mitochondria-mediated pathways. PLoS ONE. 2012, 6: e27441-View ArticleGoogle Scholar
- Zhang Z, Teruya K, Eto H, Shirahata S: Induction of apoptosis by low-molecular weight fucoidan through calcium- and caspase-dependent mitochondrial pathways in MDA-MB-231 breast cancer cells. Biosci Biotechnol Biochem. 2012, 77: 235-242.View ArticleGoogle Scholar
- Zhang Z, Teruya K, Yoshida T, Eto H, Shirahata S: Fucoidan extract enhances the anti-cancer activity of chemotherapeutic agents in MDA-MB-231 and MCF-7 breast cancer cells. Marine Drugs. 2013, 11: 81-98. 10.3390/md11010081.PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.