Intestinal inflammation significantly increases the risk of colorectal cancer development. In addition, gut microbial imbalance and impaired intestinal barrier are key to this inflammatory process. Under normal circumstances, gut microbes maintain a dynamic balance. Disrupting this balance can lead to an increase in harmful bacteria, which can worsen inflammation in the intestines. Repeated cycles of exposure to inflammatory damage and epithelial regeneration may contribute to intestinal inflammation.
Fucoidan, a type of sulfated polysaccharide, is the most potent pharmacological component found in seaweeds such as S. fusiforme. Fucoidan, a natural compound found in seaweed, has been found to have no harmful effects on normal cell lines like 293T and FHC, which are normal human colon epithelial cells. However, it exhibits cytotoxic properties against different types of cancer cells by effectively inhibiting their proliferation and arresting the cell cycle. In addition, fucoidan plays a role in stabilizing the composition of the intestinal microbial community in mice. There has been a lack of research on the effects of fucoidan extracted from S. fusiforme on colorectal cancer (CRC) so far, and this study seeks to bridge that gap.
In this blog, I would like to share the study, “Inhibition of the Occurrence and Development of Inflammation-Related Colorectal Cancer by Fucoidan Extracted from Sargassum fusiforme” by Xiang Li et al. According to the study mentioned earlier, fucoidan at various concentrations was found to reverse the inflammation caused by lipopolysaccharide in FHC cells, which are normal human colonic epithelial cells.
First, to investigate the cytotoxic effect of fucoidan on normal colon cells, they treated normal colon epithelial cells (FHC) with 0, 50, 100, 250, 500, 750, and 1000 μg mL–1 fucoidan, and examined the viability of FHC after 24, 48, and 72 hours of fucoidan treatment using MTT proliferation assay. The non-cytotoxic effect of fucoidan on FHC cells was confirmed as shown in Figure 1. The experimental results revealed that this treatment not only successfully reduced LPS-induced inflammation in FHC cells, as depicted in Figure 1B, but it also displayed remarkable efficacy in alleviating the pathological state of colitis mice, as evidenced by the data presented in Figure 2. The treatment demonstrated its ability to down-regulate the expression levels of related inflammatory factors in intestinal tissues, as observed in Figure 3A, B.
And 16S rDNA sequence analysis demonstrated that the DSS-induced cecal composition in mice was different from that in normal mice. The results indicate that fucoidan extracted from S. fusiforme can suppress inflammation and improve intestinal microecology both in vitro and in vivo.
Prolonged intestinal inflammation can damage multiple barriers and lead to CRC. The use of H&E staining in the study allowed for a clear visualization of the detrimental effects of colitis on the normal epithelial structure of colonic tissues in mice. Furthermore, the application of Alcian blue staining provided evidence of a significant decrease in mucin secretion by goblet cells. However, mice with colitis after treatment with fucoidan showed a healthier appearance, and conditions such as weight loss and diarrhea were significantly improved. In addition, the histological morphology of intestinal tissues tended to be normal. When compared to the control group, the treatment group of mice displayed a more intact mucus barrier and a more consistent microbial composition.
In order to better understand the impact of fucoidan on inflammation and cancer prevention, we carried out additional research to investigate how it inhibits the development of inflammation-associated colorectal cancer (CRC). The fucoidan extracted from S. fusiforme underwent testing and was found to be non-toxic to FHC cells. This confirms its potential as a safe dietary supplement for preventing and treating the disease. Therefore, researchers carried out related functional tests in CRC cell lines and found that fucoidan had the effect of inhibiting the colony formation of DLD-1 and SW480.
The research also confirmed that fucoidan could promote cell apoptosis and arrest the cell cycle at the G0/G1 phase. To further explore its molecular mechanism of action, the study verified the related functional proteins through WB. According to the results, the concentration of fucoidan had a suppressive effect on the expression levels of cell cycle-related proteins, including Cdk2, in DLD-1 and SW480 cells. Meanwhile, the apoptosis-related proteins cleaved PARP, cleaved caspase 3, and Cyt-c increased with increasing fucoidan concentration.
To further verify the inhibitory effect of S. fusiforme-derived fucoidan on CRC development in vivo, a mouse model of CRC was established and simultaneously intervened by oral administration of S. fusiforme-derived fucoidan. The study demonstrated that administering fucoidan significantly mitigated the formation of tumors in the colon of the mice. The levels of highly expressed cycle-related proteins in tissues of mice in the model group were also significantly decreased by fucoidan intervention. S. fusiforme can inhibit the development process of CRC in mice through cycle-related proteins.
In tissues of mice affected by CRC, the relative expression of inflammation-mediating p-STAT3 protein and the relative mRNA expression of inflammatory factors IL-6, IL-1β, and TNF-α were significantly increased in the model mice. The presence of Fucoidan resulted in a significant decrease in the expression of proteins and factors associated with inflammation. The STAT3-mediated pathway plays a crucial role in modulating the functions of apoptosis and proliferation in cancer cells. Recent studies have provided compelling evidence indicating that the administration of fucoidan derived from S. fusiforme can elicit a series of tumor-suppressing effects by effectively targeting the STAT3 pathway.
Based on these findings, it can be inferred that fucoidan has a significant preventive effect on colitis-associated colorectal cancer.
Source: J Agric Food Chem. 2022 Aug 3; 70(30): 9463–9476. doi: 10.1021/acs.jafc.2c02357