According to the American Cancer Society, the estimated number of new cancer cases and deaths in 2022 will likely be 1.9 million with new cases and 609,360 deaths in the United States alone.
Among them, colorectal cancer known for a low survival rate has affected many people regardless of gender. On a positive note, Fucoidan is attracting attention as having various benefits, including suppressing cancer cell proliferation. It is mainly composed of sulfated fucose in brown algae and is a naturally occurring component with no side effects in cancer treatment. Fucoidan is affected by structural factors such as sugar composition, the number of sulfate groups and their binding positions, and molecular weight. It is known to be effective against cancer cells.
However, it is yet to be known which protein the Fucoidan will work and function on. So, in this blog, I would like to introduce a study “In silico identification of potential target protein for fucoidan against colon cancer in rats” by V Ramakrishnan et al. Which investigated the specific type of proteins in colon cancer cells that are targeted by Fucoidan. The study examined a protein in colorectal cancer cells Fucoidan targets in silico (on a personal computer).
First, the 3D structure of Fucoidan was determined from the PubChem database. Next, they searched the UniProt database for genes for proteins targeting Fucoidan in colon cancer cells and selected seven rat genes: Akt-1, Kdr, Pi3k, Bcl2, Pcna, Pten, and Bax. To explain each gene, Akt-1 is a gene that is also called a trigger for cancer and inhibits cell programmed death (apoptosis). There is also a report that metastasis was suppressed when Kdr was hampered by a gene involved in angiogenesis. Pi3k is a gene involved in cell survival and death and is often mutated in cancer cells. Bcl2 is a gene that plays an essential role in promoting cell survival and inhibiting apoptosis, and an abnormal increase in this protein has been observed in cancer cells. Pcna is a gene in DNA replication expressed in various cancers. Pten is a tumor suppressor gene, and abnormalities are found in multiple cancers.
Bax is a gene that regulates apoptosis and is also a target for cancer treatment. The structure of proteins made from these genes was converted to 3D using the Swiss Model, and the homology with existing structural data was investigated. The homology of 80% or more is high (Romanchndran prot value), but all seven selected this time were 80% or more. (See Table 1) Next, when the protein-compound (Fucoidan) complex structure was analyzed by evaluating seven gene groups of PyRx software, the binding affinity between Fucoidan and Akt-1 was the highest (-6.1 Kcal/mol). The three-dimensional structures of Fucoidan and Akt-1, which have the highest binding relationship, are shown in 2D and 3D. (See Figures. 1 and 2)
In this study, we found a protein with a binding affinity for Fucoidan and a high relationship for Akt-1. The results are expected to be applied to cancer treatment, such as future research on functional elucidation and drug development.
