**1. Introduction**

Fucoidan is a water-soluble heteropolysaccharide, derived mostly from brown algae, such as *Fucus vesiculosus* (Figure 1) [1–5]. Recent studies have shown that the research on fucoidan mainly focuses on two aspects—one is to explore ways to increase the yield of fucoidan [6–9], while the other is to explore the various pharmacological activities of fucoidan [10–12], including anti-inflammatory [13,14], anti-tumor, anti-virus, hypolipidemic, antithrombotic, and so on [15], but less research exists on its mechanism. Owing to the characteristics of high incidence and high mortality of tumor, the prevention and treatment of tumor has become a global research trend. Fucoidan can exert anti-tumor e ffects mainly by inducing apoptosis [16,17], arresting cell cycle [18], inhibiting cell migration [18–20], and so on.

**Figure 1.** Fucoidan structure from *Fucus vesiculosus*.

Studies have shown that fucoidan can induce apoptosis [16]. There are two main apoptotic pathways currently studied. One is the extrinsic pathway, the death receptor pathway, which activates apopain in cells through extrinsic signal transduction [21]; the TRAIL receptor directly recruits procaspase-8, which is activated to form caspase-8, and then activates downstream effector molecules. The other is the intrinsic pathway [21,22], the mitochondrial pathway, where external stimulation leads to the enhancement of mitochondrial outer membrane permeability and apoptosis-related proteins in the mitochondrial inner. Moreover, outer membrane spaces, such as cytochrome C, form apoptosome with apaf-1; activate cascades; and further activate caspase -3, -6, and -7. Both ways can activate the downstream effector molecule caspase, which may lead to the activation of nuclease and the degradation of important proteins [23]. If the activated caspase-8 is sufficient, caspase-3 will be activated directly to induce cell apoptosis through the receptor; if the activated caspase-8 is insufficient, caspase-8 will activate the mitochondrial pathway [24,25]. In this study, the receptor of fucoidan in the process of inducing HT-29 cell apoptosis was determined at the level of gene and protein, determining that the extrinsic pathway was involved in the process of cell apoptosis; at the same time, it was found that fucoidan could affect the mitochondrial membrane potential and induce cell apoptosis through the mitochondrial pathway.

Apoptosis is usually mediated by a variety of signaling pathways, including NF-kB, PI3K, JNK, and so on [26–29]. The activation of JNK is stress-induced and plays an important role in the process including cell proliferation, differentiation, and tumor transformation.

In this study, we found that fucoidan can affect the migration, cycle, and apoptosis of HT-29 cells, and the effect of inducing apoptosis of HT-29 cells was the most significant. Thus, the purpose of this study was to explore the receptor and mechanism of fucoidan-induced apoptosis in HT-29 cells preliminarily. On one hand, it can lay a theoretical foundation for the application of fucoidan in dietary supplements and drugs; on the other hand, it can provide research support for the high-value development of kelp resources.
