The Protective and Immunomodulatory Effects of Fucoidan Against 7,12-Dimethyl benz[a]anthracene-Induced Experimental Mammary Carcinogenesis Through the PD1/PDL1 Signaling Pathway in Rats

Abstract

Fucoidan is a sulfated polysaccharide that is extracted from brown algae seaweed. This study was designed to evaluate the protective and immunomodulatory effects of dietary fucoidan on 7,12-dimethyl benz[a]anthracene (DMBA)-induced experimental mammary carcinogenesis in rats. Sixty Sprague-Dawley rats were randomly assigned to four equal groups: the control group (control group), the cancer model group (model group), and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg/kg·body weight, respectively. We found that fucoidan treatment decreased the tumor incidence and mean tumor weight and prolonged the tumor latency. Flow cytometric analyses revealed that the number of blood natural killer cells was higher after fucoidan treatment and that the proportions of CD4 and CD8 T cells were also increased. The serum levels of interleukin (IL)-6, IL-12p40, and interferon (IFN)-γ were higher in the rats treated with fucoidan compared to those of model rats. Moreover, the percentage of CD3+ Foxp3+ regulatory T cells in the blood and the levels of IL-10 and transforming growth factor β in the serum were lower in the rats treated with fucoidan. Furthermore, fucoidan treatment decreased the expression of Foxp3 and programmed cell death 1 ligand 1 (PDL1) in tumor tissues. The levels of p-phosphatidyl inositol kinase 3 and p-AKT in tumor tissues were also lower than those of model rats. These results suggest that a fucoidan-supplemented diet can inhibit DMBA-induced tumors in rats. This study provides experimental evidence toward elucidating the immune enhancement induced by fucoidan through the programmed cell death 1/PDL1 signaling pathway. The immunomodulatory effect is one of the possible mechanisms of the protective effect of fucoidan against mammary carcinogenesis.

The Effect of Fucoidan from the Brown Alga Fucus evanescence on the Activity of α-N-Acetylgalactosaminidase of Human Colon Carcinoma Cells

“…It has been shown, that ionogenic polysaccharides from an edible brown alga, Hijikia fusiforme (Hijiki), have a possible enhancing activity for macrophage-dependent suppression against tumor cell growth [ 55 ]. Finally, more recently, it has been shown that the immunomodulating effect is one of the possible mechanisms of the protective action of fucoidan against carcinogenesis of the breast [ 56 ].…”

Protective effect and mechanism of fucoidan on intestinal mucosal barrier function in NOD mice

“…The mice were free to access the standard dry diet as well as tap water ad libitum. All aspects of the experiment were conducted according to the Guide for the Care, and Use of Laboratory Animals (issued by the Ministry of Science and Technology of the People's Republic of China in 2006 [398]) and this research was approved by the Review Committee for the Use of Human or Animal Subjects of the Medical College of Qingdao University (Shi et al, 2017;Xue et al, 2017).…”

Haimufang decoction, a Chinese medicine formula for lung cancer, arrests cell cycle, stimulates apoptosis in NCI-H1975 cells, and induces M1 polarization in RAW 264.7 macrophage cells

“…Brown algae Sargassum fusiforme which dosage is twice than others, contains abundant polysaccharides such as fucoidan, algin, and so on. There are some evidences that fucoidan exerts anticancer activity through immune regulation [9,10]. In addition to polysaccharides, HMF contains quite a few of alkaloids, including dibenzylisoquinoline alkaloids dauricine and daurisoline which derived from Mertispermum dauricum, and steroid alkaloids solasonine and solamargine from Solanum nigrum.…”