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Gastrointestinal mucositis (GIM), induced by chemotherapy, is associated with alterations in the function of the intestinal barrier due to the potential damage induced by anti-cancer drugs on the epithelial cells. The Paneth cells, an important epithelial lineage in the intestine, contribute to the innate immunity by releasing antimicrobial proteins onto the mucosal surfaces. Polysaccharide, as a widely used immunomodulatory nutrient, was reported to have an effect of modulating the intestinal immune system. However, the effect of dietary polysaccharides in protecting the Paneth cells from injuries induced by chemotherapy was poorly investigated. In the current study, with a mouse model of cyclophosphamide (Cy)-induced gastrointestinal injury, the polysaccharide extracted from the ink of Ommastrephes bartrami (OBP) were found to protect the mouse Paneth cells from chemotherapeutic injury. Ommastrephes bartrami polysaccharide (OBP) treatment could enhance the mRNA expression of antimicrobial proteins in the Paneth cells, such as lysozyme, Ang4, Defa-5, and sPLA 2 . The increased production of the microbicidal proteins in the Paneth cells was dependent on the relatively highly developed endoplasmic reticulum (ER) structure but was not dependent on the increase in the quantity of the ER. The Ommastrephes bartrami polysaccharide (OBP) activated the IRE-1 mediated XBP-1s pathway to cope with antimicrobial protein secretion. Our results may have important implications with regard to the role of OBP in chemotherapy-induced Paneth cell injury in intestinal disorders involving inflammation and infection. [ABSTRACT FROM AUTHOR]

Purpose Fucoidan, a complex, sulfated polysaccharide obtained from brown seaweed, exerted anticancer activity through the down-regulation of β-catenin signaling in mouse breast cancer cells in our previous study. This study examines the anti‐cancer effects of fucoidan as well as its underlying molecular mechanisms in the human triple negative breast cancer (TNBC) cell line and in 7,12-dimethylbenz[a]anthracene (DMBA)-induced experimental mammary carcinogenesis in rats. Methods in vitro studies, fluorescent staining, flow cytometry and Western blotting were performed to analyze apoptosis and protein expression in human breast cancer MDA-MB-231 cells. In vivo intervention experiments were conducted with Sprague Dawley (SD) rats with DMBA-induced breast cancer. Tumor volumes and weights were measured. Results in vitro fucoidan treatment inhibited proliferation and induced apoptosis in MDA-MB-231 cells. Western blotting detected that Cyt C and Smac were released into the cell cytoplasm and that caspase-3 and caspase-9 were activated in MDA-MB-231 cells. The levels of AIF and EndoG were significantly increased in the cytoplasm and in the nuclei by fucoidan. These data show that fucoidan induced caspase-dependent and caspase-independent apoptosis. Moreover, fucoidan treatment down-regulated the expression of Bid, Bcl-2 and Bcl-xl and up-regulated the level of Bax. In vivo, fucoidan supplementation decreased the mean tumor weight. Discussion: Results from the in vivo and in vitro experiments both showed that fucoidan decreased the levels of p-PI3K, p-AKT and p-GSK-3β (Ser9) in breast cancer. The level of β-catenin was also decreased. These results suggest that fucoidan can inhibit MDA-MB-231 human breast cancer cells and DMBA-induced tumors in rats by down-regulating the PI3 K/AKT/GSK3β pathway. This study provides experimental evidence that elucidates the mechanism of antitumor effect of fucoidan and clarifies the mechanism of the effect of fucoidan on the regulation of β-catenin. [ABSTRACT FROM AUTHOR]