Effects of Fucoidan and Chemotherapeutic agent combinations on Malignant and Non-Malignant breast cell lines

Abstract

Background Breast cancer is currently one of the most common malignancies in women. Fucoidan (FUC) is a natural polysaccharide with anticancer properties. Despite a number of in vitro and in vivo studies reporting the efficacy of fucoidan in treating various cancers, few studies have measured the efficacy of fucoidan in combination with cancer drugs. Drugs like cisplatin, doxorubicin and taxol are important in breast cancer treatment. However, in recent years, supplements have gained importance in its treatment. Fucoidan, a sulfated polysaccharide mainly found in brown algae and seaweed, is a new candidate for breast cancer therapy because of its antitumour activity. This study was aimed at determining the cytotoxic, apoptotic and cell cycle distribution effects of fucoidan and its synergistic and/or antagonistic effects in combination with cisplatin, doxorubicin and taxol in the breast cancer cell line, MCF-7, relative to the normal MCF-12A non-malignant breast epithelial cell line. Methods The IC50 value of each agent was obtained against MCF-7 and MCF-12A cells using the MTTcytotoxicity assay. Apoptosis was determined with the Annexin VFITC/PI assay, Active Caspase-3/-7, and -9 and cell cycle assays, followed with Hoechst-33342 staining. MCF-12A non-cancerous epithelial breast cells was used as the control. Results Overall, fucoidan significantly increased the cytotoxic effect of the chemotherapeutic agents. Consistently, costimulation of MCF-7 cells with any chemotherapeutic agent in the presence of fucoidan further increased apoptosis induction, caspase-3/-7 and caspase-9 activation, particularly, in cisplatin- and taxol-challenged cells more than fucoidan-doxorubicin compared to untreated controls. Furthermore, fucoidan treatment resulted in G1 phase cell cycle arrest of MCF-7 cells and accumulation of the sub-G1 population as revealed by flow cytometry. Fucoidan-drug combinations strongly induced the accumulation of MCF-7 cells in the G2/M and sub-G1phase. In contrast, no significant differences for cytotoxicity and apoptosis or cell cycle profile were found between fucoidan treated and untreated MCF-12A cells. Conclusions Fucoidan is an effective antitumour agent either alone or in combination with cisplatin, doxorubicin and taxol in MCF-7 breast cancer cells. These findings suggest that fucoidan is a candidate natural product for breast cancer combination therapies. Further studies are required to evaluate cancer-specific and fraction-specific mechanisms of fucoidan for translation into in vivo tumour models.