Fucoxanthinol (FxOH), the main metabolite of the marine carotenoid fucoxanthin, exerts anti-cancer effects. However, fragmentary information is available on the growth-inhibiting effects of FxOH on breast cancer (BC). We investigated the growth-inhibiting effects of FxOH on human BC cells (MCF-7 and MDA-MB-231 cells), and the underlying mechanisms, differently from previous studies, by using comprehensive transcriptome analysis. The molecular mechanisms of FxOH were evaluated using flow cytometry, microarray, Western blotting, and gene knockdown analyses. FxOH (20 μM) significantly induced apoptosis in MCF-7 and MDA-MB-231 cells. Transcriptome analysis revealed that FxOH modulated the following 12 signaling pathways: extracellular matrix (ECM), adhesion, cell cycle, chemokine and cytokine, PI3K/AKT, STAT, TGF-β, MAPK, NF-κB, RAS/Rho, DNA repair, and apoptosis signals. FxOH downregulated the levels of laminin β1, integrin α5, integrin β1, integrin β4, cyclin D1, Rho A, phosphorylated (p)paxillin (Tyr³¹), pSTAT3(Ser⁷²⁷), and pSmad2(Ser^465/467), which play critical roles in the 12 signaling pathways mentioned above. Additionally, FxOH upregulated the levels of pERK1/2(Thr²⁰²/Tyr²⁰⁴) and active form of caspase-3. Integrin β1 or β4 knockdown significantly inhibited the growth of MCF7 and MDA-MB-231 cells. These results suggest that FxOH induces apoptosis in human BC cells through some core signals, especially the ECM–integrins axis, and the downstream of cell cycle, STAT, TGF-β, RAS/Rho, MAPK, and/or DNA repair signals.

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation and its treatment varies widely; however, when inflammation is high, a complete nutrient containing pre-digested elemental diet (ED) is used to preserve the intestinal tract. In this study, we investigated the mechanisms underlying the effectiveness of EDs for IBD using mice. C57BL/6 mice were orally treated with the ED (5 mL/day) and its ingredient L-tryptophan (Trp) (1–100 mg/kg), respectively. Flow cytometry analysis revealed that treatment with the ED and Trp (10 and 100 mg/kg) significantly increased the percentage of splenic CD4+-/CD25+-/Foxp3+ regulatory T cells (Tregs). In the 2% DSS-induced colitis-mouse model, Trp administration (100 mg/kg) led to a significant decrease in TNF-α and increase in IL-10 in the serum as well as a significant decrease in the inflammation score. Furthermore, the aryl hydrocarbon receptor (AhR) agonistic activity, which is a key function of Treg induction, of Trp and 15 Trp metabolites was characterized using a highly sensitive DR-EcoScreen cell assay. Five Trp metabolites, including L-kynurenine, acted as AhR agonists, while Trp did not. Taken together, these results suggest that the ED treatment has a Trp-dependent immunoregulatory effect, and several Trp metabolites that activate the AhR might contribute to induction of remission in patients with IBD.