Improved Innate Immune Responses by Frondanol A5, a Sea Cucumber Extract, Prevent Intestinal Tumorigenesis

Abstract

Sea cucumbers are a source of anti-bacterial, anti-inflammatory, and anti-cancer compounds. We show that sea cucumber extract Frondanol® A5 is capable of enhancing innate immune responses and inhibiting intestinal tumors in APCMin/+ mice. APCMin/+ mice were fed semi-purified diets containing 0, 250, or 500 ppm Frondanol®A5 for 14 weeks before we assessed intestinal tumor inhibition. Dietary Frondanol® A5 suppressed small intestinal polyp sizes and formation up to 30% (p<0.02) in males and up to 50% (p<0.01) in females. Importantly, 250 and 500 ppm Frondanol® A5 diet suppressed colon tumor multiplicities by 65% (p<0.007) and 75% (p<0.0001), compared with untreated male APCMin/+ mice. In female APCMin/+ mice, both dose levels of Frondanol® A5 suppressed colon tumor multiplicities up to 80% (p<0.0001). Isolated peritoneal macrophages from treated mice showed increased phagocytosis efficiency (Control 24% Vs treated 50%; p<0.01) and an increase in GILT mRNA expression, indicating increased innate immune responses by these cells in treated animals. Similarly, we observed an increase in GILT expression in treated tumors, compared with untreated tumors. Furthermore, an increase in GCSF cytokine, a decrease in inflammatory cytokines and marker 5-LOX, its regulator FLAP, proliferation (PCNA), and angiogenesis (VEGF) markers was observed in treatment groups. These data suggest that Frondanol® A5 decreased inflammatory angiogenic molecules and increased GILT expression and macrophage phagocytosis. These decreases may have improved the innate immune systems of the treated mice, thus aiding in inhibition of intestinal tumor formation. These results suggest that Frondanol® A5 exhibits significant chemopreventive potential against intestinal tumorigenesis.

Effectiveness of gold sea cucumber (Stichopus hermanii) extracts in accelerating the healing process of oral traumatic ulcer in rats

“…Based on the literature suggested that existing glycosaminoglycan content in sea cucumbers may play a role as a modulator of inflammation such as macrophage, become more active. 10 Glycosaminoglycans (GAGs) in gold sea cucumber, participate in a variety of biological processes including cell-matrix interactions and activation of chemokines, enzymes and growth factors. 11 There are a variety of growth factors in the extracellular matrix (ECM), including members of the transforming growth factor-beta (TGF-β) superfamily, and vascular endothelial growth factor (VEGF).…”

“…The release of TGF-β led to an increase in collagen synthesis. 10 The process of wound healing will occur faster, and clinically can be shown by the decrease of ulcer diameter.…”

Therapeutic Application of Diverse Marine-derived Natural Products in Cancer Therapy

“…In addition, Ds-echinoside A has also been shown to inhibit proliferation of human hepatocellular carcinoma cells, and to suppress cell adhesion, migration, invasion, and angiogenesis via regulation of MMP9, TIMP-1, and VEGF expression (65). Frondanol A5 is an isopropyl alcohol/water extract derived from Cucumaria frondosa and its application has been shown to inhibit cell growth via modulation of p21WAF1/CIP and Cdc25c, thus inducing apoptosis of human colon cancer cells (66), as well as innate immune responses and inhibiting the growth of intestinal tumors in mice model (67). Frondanol A5P, a polar extract isolated from Cucumaria frondosa.…”

Sea Cucumbers Metabolites as Potent Anti-Cancer Agents

“…In female mice, both doses produced 80% inhibition of CTs. We reported an increase in immune responses in treated animals, in which the isolated macrophages showed increased phagocytosis and GILT expression, compared with untreated animals [ 31 ] ( Table 1 ) ( Figure 3 ). These data suggest that Frondanol A5 has the potential to improve innate immune responses during intestinal tumor formation and could be further developed for prevention and treatment.…”

“…Sea cucumbers consist of vitamins, minerals, cerebrocides, peptides, and lectins, and also contain unique molecules, such as sulfated polysaccharides, 12-methyltetradecanoic acid (12-MTA), philinopside E, triterpene glycoside compounds, glycosaminoglycan, and chondroitin sulfates [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. In sufficient quantities, these unique compounds are known to possess anti-microbial, anti-oxidant, anti-angiogenic, anti-inflammatory, immunomodulatory, and anti-tumoral properties [ 28 , 29 , 30 , 31 ] ( Figure 1 ). As supplements, these sea cucumber extracts have been shown to suppress inflammation and increase innate immune responses.…”