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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.

SUBMITTER: Janakiram NB

PROVIDER: S-EPMC4839268 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Improved innate immune responses by Frondanol A5, a sea cucumber extract, prevent intestinal tumorigenesis.

Janakiram Naveena B NB Mohammed Altaf A Bryant Taylor T Lightfoot Stan S Collin Peter D PD Steele Vernon E VE Rao Chinthalapally V CV

Cancer prevention research (Philadelphia, Pa.) 20150205 4

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 ...[more]

PMID: 25657017

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Project description:BackgroundAmong deuterostomes, the regenerative potential is maximally expressed in echinoderms, animals that can quickly replace most injured organs. In particular, sea cucumbers are excellent models for studying organ regeneration since they regenerate their digestive tract after evisceration. However, echinoderms have been sidelined in modern regeneration studies partially because of the lack of genome-wide profiling approaches afforded by modern genomic tools.For the last decade, our laboratory has been using the sea cucumber Holothuria glaberrima to dissect the cellular and molecular events that allow for such amazing regenerative processes. We have already established an EST database obtained from cDNA libraries of normal and regenerating intestine at two different regeneration stages. This database now has over 7000 sequences.ResultsIn the present work we used a custom-made microchip from Agilent with 60-mer probes for these ESTs, to determine the gene expression profile during intestinal regeneration. Here we compared the expression profile of animals at three different intestinal regeneration stages (3-, 7- and 14-days post evisceration) against the profile from normal (uneviscerated) intestines. The number of differentially expressed probes ranged from 70% at p < 0.05 to 39% at p < 0.001. Clustering analyses show specific profiles of expression for early (first week) and late (second week) regeneration stages. We used semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) to validate the expression profile of fifteen microarray detected differentially expressed genes which resulted in over 86% concordance between both techniques. Most of the differentially expressed ESTs showed no clear similarity to sequences in the databases and might represent novel genes associated with regeneration. However, other ESTs were similar to genes known to be involved in regeneration-related processes, wound healing, cell proliferation, differentiation, morphological plasticity, cell survival, stress response, immune challenge, and neoplastic transformation. Among those that have been validated, cytoskeletal genes, such as actins, and developmental genes, such as Wnt and Hox genes, show interesting expression profiles during regeneration.ConclusionOur findings set the base for future studies into the molecular basis of intestinal regeneration. Moreover, it advances the use of echinoderms in regenerative biology, animals that because of their amazing properties and their key evolutionary position, might provide important clues to the genetic basis of regenerative processes.

Project description:The gut microbiome has far-reaching effects on host organism health, so understanding the processes that underlie microbial community assembly in the developing gut is a current research priority. Here, a holothurian (also known as sea cucumber; phylum Echinodermata) host is explored as a promising model system for studying the assembly of the gut microbiome. Holothurians have a unique capacity for evisceration (expulsion of the internal organs), followed by rapid regeneration of the gut, decoupling host ontogeny from gut tissue development and permitting experimental manipulation of the gut microbiome in mature host individuals. Here, evisceration was induced in the sea cucumber Sclerodactyla briareus, and regenerating stomach and intestine microbiomes were characterized before and on days 0, 13, 17, and 20 after evisceration using Illumina sequencing of 16S rRNA genes. Regenerating stomach and intestine tissues had microbial communities significantly different from those of mature tissues, with much higher alpha diversity and evenness of taxa in regenerating tissues. Despite immersion in a diverse pool of sediment and seawater microbes in flowthrough seawater aquaria, regenerating gut microbiomes differed at each stage of regeneration and displayed a highly similar community structure among replicates, providing evidence for deterministic host selection of a specific microbial consortium. Moreover, regenerating gut tissues acquired a microbiome that likely conferred energetic and immune advantages to the sea cucumber host, including microbes that can fix carbon and degrade invading pathogens.IMPORTANCE The gut microbiome is pertinent to many aspects of animal health, and there is a great need for natural but tractable experimental systems to examine the processes shaping gut microbiome assembly. Here, the holothurian (sea cucumber) Sclerodactyla briareus was explored as an experimental system to study microbial colonization in the gut, as S. briareus individuals have the ability to completely eviscerate and rapidly regenerate their digestive organs. After induced evisceration, microbial community assembly was characterized over 20 days in regenerating animals. This study demonstrated that colonization of the sea cucumber gut was deterministic; despite immersion in a diverse consortium of environmental microbes, a specific subset of microbes proliferated in the gut, including taxa that likely conferred energetic and immune advantages to the host. Sea cucumbers have the potential to revolutionize our understanding of gut microbiome assembly, as rapid and repeatable gut tissue regeneration provides a promising and tractable experimental system.

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Improved innate immune responses by Frondanol A5, a sea cucumber extract, prevent intestinal tumorigenesis.

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Improved innate immune responses by Frondanol A5, a sea cucumber extract, prevent intestinal tumorigenesis.

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