Improved innate immune responses by Frondanol A5, a sea cucumber extract, prevent intestinal tumorigenesis.
Improved innate immune responses by Frondanol A5, a sea cucumber extract, prevent intestinal tumorigenesis.
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DOI：
10.1158/1940-6207.capr-14-0380
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Rao CV
中科院分区：
文献类型：
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作者：
Janakiram NB;Mohammed A;Bryant T;Lightfoot S;Collin PD;Steele VE;Rao CV
海参是抗菌，抗炎和抗癌化合物的来源。我们发现海参提取物Frondanol® A5能够增强APCMin/+小鼠的先天免疫应答并抑制肠道肿瘤。APCMin/+小鼠喂食含有0、250或500 ppm Frondanol®A5的半纯化饮食14周，然后我们评估肠道肿瘤抑制。膳食Frondanol® A5抑制小肠息肉大小和形成，在雄性中高达30%（p<0.02），在雌性中高达50%（p<0.01）。重要的是，与未处理的雄性APCMin/+小鼠相比，250和500 ppm Frondanol® A5饮食抑制结肠肿瘤多重性65%（p<0.007）和75%（p<0.0001）。在雌性APCMin/+小鼠中，两种剂量水平的Frondanol® A5抑制结肠肿瘤多重性高达80%（p<0.0001）。从处理的小鼠分离的腹膜巨噬细胞显示增加的吞噬效率（对照24%Vs处理的50%; p<0.01）和GILT mRNA表达的增加，表明这些细胞在处理的动物中增加的先天免疫应答。类似地，我们观察到与未处理的肿瘤相比，在处理的肿瘤中GILT表达增加。此外，在治疗组中观察到GCSF细胞因子增加，炎性细胞因子和标记物5-LOX、其调节因子FLAP、增殖（PCNA）和血管生成（VEGF）标记物减少。这些数据表明，Frondanol® A5减少了炎性血管生成分子，并增加了GILT表达和巨噬细胞吞噬作用。这些减少可能改善了治疗小鼠的先天免疫系统，从而有助于抑制肠道肿瘤形成。这些结果表明，Frondanol® A5对肠道肿瘤发生表现出显著的化学预防潜力。
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.