Colorectal cancer has become an increasing global health concern. It is a leading cause of mortality in men and women, and affects more than one million people worldwide annually. The features of the disease usually occur progressively over a protracted period owing to increased genomic instability, which leads to the upregulation of oncogenes and the downregulation of tumor suppressor genes.
Studies have shown that major intracellular signaling pathways are altered during tumorigenesis, leading to cell proliferation and survival. The inhibition of proliferation and induction of apoptosis in tumor cells is a strategy used in antitumor therapy. The balance between proliferation and apoptosis signaling pathways controls tumor pathogenesis.
What is fucoidan?
A number of sulfated polysaccharides, which are natural products present in Fucoidan, exert potent antitumor activity by inducing cell cycle arrest and apoptosis in several tumor cell lines. Fucoidans are a class of fucose-enriched sulfated polysaccharides and are found in the extracellular matrix of brown algae.
Fucoidans have various biological activities, including antiviral, anticoagulant, anti-inflammatory, immunomodulatory, anti-angiogenic, and anti-adhesive. Furthermore, fucoidan induces antitumor effects in several tumor cell lines, both in vitro and in vivo.
Effects of fucoidan on Colorectal cancer
Efficacy of Low-Molecular-Weight Fucoidan as a Supplemental Therapy in Metastatic Colorectal Cancer Patients: A Double-Blind Randomized Controlled Trial 
Fucoidan is an aggregate name for algal fucose-enriched sulfated polysaccharides extracted from the extracellular matrix of brown, green, and red seaweeds. Fucoidan was first introduced by Dr. Kylin in 1913 while analyzing the reason behind the lower incidence of cancer in Okinawa, Japan. Since then, more than 1400 studies focusing on its biological activities have been conducted.
In particular, the antioxidant, anticancer, anti-inflammatory, and anti-proliferative activities of fucoidan have attracted considerable attention. Therefore, fucoidan has become a widely used food supplement in Asia, especially in Japan, China, Taiwan, and Australia.
According to previous in vitro and animal studies, Fucoidan has a cytotoxic effect in the HCT-15 colon cancer cell line. Fucoidan also inhibits the migration and proliferation of HT-29 human colon cancer cells via the phosphoinositide-3 kinase, Akt, mechanistic target of rapamycin pathways.
It was demonstrated that fucoidan represses cancer metastasis by inhibiting vascular endothelial growth factor and matrix metalloproteinases (MMPs) in Lewis tumor-bearing mice.
This is the first randomized, double-blind, controlled trial evaluating the efficacy of Low-Molecular-Weight Fucoidan as a supplemental therapy in patients with metastasis colon cancer.
The research results demonstrate the advantages of Low-Molecular-Weight Fucoidan in improving the disease control rate. This study can provide insights into the development of cancer treatments, particularly in the combination of natural or herbal products with chemo target agents.
Fucoidans and Drug Resistance in Cancer 
There are many types of cancer treatments, including surgery, radiation, chemotherapy, hormone therapy and, more recently, target therapy (e.g., chemokine receptors), stem cells transplantation, and immunotherapy.
One of the major complications in cancer treatment is the appearance of chemotherapy resistance, which is defined as the development of innate or acquired ability by cancer cells to evade the effects of chemotherapeutics.
Some cancer cells are intrinsically resistant to chemotherapy and others are able to develop a resistance phenotype, either by their own characteristics as tumor cells or by external conditions such as the tumor microenvironment. For instance, repeated chemotherapeutic stimulation can induce pro-survival biological changes in tumor cells, allowing them to evade cell death under drug pressure by using host or tumor-related factors.
Most chemotherapeutic agents in cancer therapy (e.g., platinum drugs, taxanes) induce cell stress on “sensitive cells” resulting in cell death mediated predominantly by the apoptosis pathway.
In this study, the fucoidan was applied as a biocompatible surfactant and surface-coating biopolymer in the fucoidan-coated photothermal nanocarrier. As a result, the biological–chemo–thermo combination treatment showed a promising therapeutic effciency against multidrug resistant breast cancer cell MCF-7 ADR both in in vitro and in vivo.
In this context, the potential mechanisms in which fucoidans can reverse the drug resistance are versatile. Fucoidans can inhibit chemokine/chemokine receptors interaction as a pre-target mechanism. The increase of cell cytotoxicity and arrest of the cell cycle demonstrates their effect on on-target mechanisms.
Fucoidan reduced proliferation and induced apoptosis in tumor tissue 
To further confirm the ability of fucoidan to induce apoptosis in vivo, immunohistochemical staining was performed on tissue sections of tumors excised from mice that were treated with various doses of fucoidan 30 days after HT29 colon cancer cell implantation.
Fucoidan treatment significantly decreased the number of PCNA (Proliferating cell nuclear antigen)-positive cells and increased the number of caspase-3-positive apoptotic cells. These results suggest that fucoidan has a strong antitumor effect in this colon cancer model and is a potent apoptosis-inducing agent in vivo.
Fucoidan inhibited angiogenesis in tumor tissue 
To investigate the effect of fucoidan on angiogenesis in vivo, we analyzed tumors by immunohistochemical staining to measure the expression of vascular endothelial growth factor. Immunoreactive vascular endothelial growth factor in the tumors decreased after fucoidan treatment.
In addition, In this study evaluated CD31 (The one of the vascular endothelial growth factors) expression in tumors. It shows that CD31 expression was reduced in the tumors of mice treated with fucoidan.
Intake of Fucoidan for Colon cancer prevention and treatment
As mentioned above, Fucoidan has immense benefits to prevent and cure colon cancer. Although Fucoidan can be collected from nature as a food resource, since it is a sea algae it is more likely to be eaten as a portion of food without knowing the exact amount and method of intake. Thus, to take proper Fucoidan, taking as a food supplement containing Fucoidan is recommended.
 Efficacy of Low-Molecular-Weight Fucoidan as a Supplemental Therapy in Metastatic Colorectal Cancer Patients: A Double-Blind Randomized Controlled Trial
 Brown Seaweed Fucoidan in Cancer: Implications in Metastasis and Drug Resistance
 Antitumor Effects of Fucoidan on Human Colon Cancer Cells via Activation of Akt Signaling