Fucoidan, extracted from wakame seaweed, has demonstrated its ability to display anticancer properties in different types of tumor cells. The positive outcome has led to its recognition as a potential candidate for cancer treatment, praised for its low toxicity. Besides previous research findings, it has been discovered that fucoidan, which is a sulfated polysaccharide obtained from wakame, can inhibit β-catenin signaling in breast cancer cells in mice, thus exhibiting promising anticancer properties.

This blog explains the anticancer effects of fucoidan and its underlying molecular mechanisms in 7,12-dimethylbenz[a]anthracene (DMBA)-induced experimental breast carcinogenesis in human triple-negative breast cancer (TNBC) cell lines and rats. Hence, I would like to share the research “Caspase-dependent and caspase-independent induction of apoptosis in breast cancer by fucoidan via the PI3K/AKT/GSK3β pathway in vivo and in vitro” by Meilan Xue et al.

The study assessed the impact of fucoidan on cell proliferation, apoptosis, and the expression of apoptosis-related proteins in MDA-MB-231 cells, aiming to determine its potential as a therapeutic agent for triple-negative breast cancer (TNBC). It was also to determine whether the apoptosis-inducing effect of fucoidan depends on caspases. The researchers started by performing in vitro studies, then moved on to conducting fluorescent staining, flow cytometry, and western blotting in order to analyze apoptosis and protein expression in human breast cancer MDA-MB-231 cells. An in vivo intervention experiment was performed using rats with DMBA-induced breast cancer. Results In vitro fucoidan treatment inhibited proliferation and induced apoptosis of MDA-MB-231 cells.

To examine the impact of fucoidan on cell viability, the researchers conducted a test using CCK-8. When treated with 6.25, 12.5, and 25 μg/mL fucoidan, the proliferation of MDA-MB-231 cells was inhibited compared to that of untreated control cells. (Figure 1A) Treatment of MDA-MB-231 cells with 25 μg/mL fucoidan for 48 and 72 hours inhibited cell viability by 56.7% and 60.0%, respectively.

The objective was to assess the apoptotic effects of fucoidan treatment by staining MDA-MB-231 cells with Hoechst 33258 dye. As shown in Figure 1B, the study showed that protein levels of the PI3K/AKT/GSK3β pathway were reduced in breast tumors.

Western blotting also detected that Cyt C and Smac were released into the cytoplasm and caspase-3 and caspase-9 were activated in MDA-MB-231 cells. AIF and EndoG levels were significantly increased in the cytoplasm and nucleus by fucoidan. These data indicate that fucoidan-induced caspase-dependent and caspase-independent apoptosis. In addition, the level of Bid, Bcl-2, and Bcl-xl expression was decreased upon fucoidan treatment, whereas the expression of Bax was increased. In vivo, fucoidan supplementation reduced mean tumor weight. The levels of p-PI3K, p-AKT, and p-GSK-3β (Ser9) in breast cancer were found to be reduced by fucoidan according to both in vivo and in vitro experimental results, and there was also a decrease in β-catenin levels. (See Figure. 2)

In this study, treatment with fucoidan inhibited proliferation and induced apoptosis in human breast cancer MDA-MB-231 cells. Supplementation of fucoidan in DMBA-induced breast cancer rats during in vivo studies showed a significant decrease in both tumor incidence and mean tumor weight. This indicated the anticancer effect of fucoidan in human triple-negative patients.

In conclusion, fucoidan effectively inhibits DMBA-induced tumors in MDA-MB-231 human breast cancer cells and rats by downregulating the PI3 K/AKT/GSK3β pathway. Experimental evidence is provided by this study to elucidate the mechanism of fucoidan’s anti-tumor effect and its effect on β-catenin.

Source: PMID: 28810530 DOI: 10.1016/j.biopha.2017.08.013