In Vitro Study of the Cytotoxic Effects of Low- and High-molecular-weight Fucoidan Extracted from New Zealand Seaweed Undaria Pinnatifida in MCF-7 and MDA-MB-231 Breast Cancer Cell Lines
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Breast cancer is known as the top cancer for women worldwide. It is estimated that every year over one million new cases of breast cancer are diagnosed and contribute largely to cancer related deaths. Chemotherapy, including neoadjuvant therapy and adjuvant therapy, is a critical part in treatment for breast cancer that impact on survival and life quality for patients. However, chemo-resistance and adverse effects occur frequently when patients receive chemotherapy or the improved target therapies. New strategies have been proposed to enhance the effects of anticancer drugs as combing them with natural dietary compounds, decreasing drug dose administered and reducing the toxicity to normal cells. Fucoidan is noticed for its anti-cancer potential in treating breast cancer as well as in many other cancers. It is a natural bioactive compound derived from brown algae that has low toxicity and multiple anti-cancer pathways, the potential of which makes it a candidate for therapeutic agent using alone or in combination with other cytotoxic drugs. Base on the molecular weight, fucoidan can be categorised into three ranges: high-molecular weight fucoidan (HMF, >300k), medium-molecular weight fucoidan (MMF, 300-10k) and low-molecular weight fucoidan (LMF, <10k). In this study, the inhibitory effects of HMF and LMF from New Zealand Undaria Pinnatifida have been studied against breast cancer. Two breast cancer cell lines, MCF-7 and MDA-MB-231, have been used in this study representing ER-positive type and triple-negative type of breast cancer. A fibroblast (HDFa) cell line has also been used in this study, representing non-cancer cells, to examine toxicity of fucoidan. By conducting MTT assays, apoptosis assay and other related mechanism assays on cancer cells, the findings in this study indicate that LMF exhibited much better inhibition on proliferation of breast cancer cells than HMF. Dose-dependent inhibition by LMF was observed in both MCF-7 and MDA-MB-231 after incubated for 48, 72 and 96 hours. MCF-7 cells are more sensitive to LMF than MDA-MB-231 by a distinction of about 20% inhibition at the highest concentration of LMF (56.6% inhibition at 200 µg/ml and 39.2% inhibition at 300µg/ml,72hrs, respectively) and time-dependent manner of inhibition was only observed in MCF-7. The IC50 of LMF to MCF-7 cells over 72 hours was determined to be about 19 µg/ml and dropped to 10.5 µg/ml after 96 hours. Induction of caspase-dependent apoptosis was observed in MDA-MB-231 cells through intrinsic apoptosis pathway alone or with the extrinsic pathway. An activation of NOS stimulated by LMF was observed in MDA-MB-231 cells at a dose-dependent manner. No obvious cytotoxicity of LMF to HDFa cells was observed by 72 hours incubation in a cell cycle assay. To conclude, LMF from New Zealand Undaria Pinnatifida showed great anti-cancer effects against these two types of breast cancer, therefore, it has great potential to be used as a therapeutic agent or a supplement to combine with other chemo-agents for treating breast cancer, even though it may not be potent enough to treat this type of cancer alone.