title: Improved innate immune responses by Frondanol A5, a sea cucumber extract, prevent intestinal tumorigenesis.
abstract: Sea cucumbers are a source of antibacterial, anti-inflammatory, and anticancer compounds. We show that sea cucumber extract Frondanol A5 is capable of enhancing innate immune responses and inhibiting intestinal tumors in APC(Min/+) mice. APC(Min/+) mice were fed semi-purified diets containing 0, 250, or 500 ppm FrondanolA5 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 APC(Min/+) mice. In female APC(Min/+) 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 G-CSF cytokine, a decrease in inflammatory cytokines and marker 5-LOX, its regulator FLAP, proliferation (PCNA), and angiogenesis (VEGF) markers were 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.
authors: Center for Cancer Prevention and Drug Development, Department of Medicine, Hem-Onc Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. cv-rao@ouhsc.edu naveena-janakiram@ouhsc.edu.
authors: Naveena B
authors: NB
authors: Janakiram
authors: Center for Cancer Prevention and Drug Development, Department of Medicine, Hem-Onc Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors: Altaf
authors: A
authors: Mohammed
authors: Center for Cancer Prevention and Drug Development, Department of Medicine, Hem-Onc Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors: Taylor
authors: T
authors: Bryant
authors: Center for Cancer Prevention and Drug Development, Department of Medicine, Hem-Onc Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors: Stan
authors: S
authors: Lightfoot
authors: Coastside Bio Resources, Deer Isle, Maine.
authors: Peter D
authors: PD
authors: Collin
authors: Division of Cancer Prevention, Chemopreventive Agent Development Research Group, National Cancer Institute, Bethesda, Maryland.
authors: Vernon E
authors: VE
authors: Steele
authors: Center for Cancer Prevention and Drug Development, Department of Medicine, Hem-Onc Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. cv-rao@ouhsc.edu naveena-janakiram@ouhsc.edu.
authors: Chinthalapally V
authors: CV
authors: Rao
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D045424:Complex Mixtures / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D017491:Genes, APC / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007124:Immunoenzyme Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D050862:Oxidoreductases Acting on Sulfur Group Donors; D010587:Phagocytosis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012616:Sea Cucumbers / Q000737:chemistry*
chemical_list: D045424:Complex Mixtures; D016207:Cytokines; C552590:Frondanol-A5P; D018836:Inflammation Mediators; D012333:RNA, Messenger; D010088:Oxidoreductases; C483811:Ifi30 protein, mouse; D050862:Oxidoreductases Acting on Sulfur Group Donors
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