Janakiram Naveena B, Mohammed Altaf, Bryant Taylor, Lightfoot Stan, Collin Peter D, Steele Vernon E, Rao Chinthalapally V
Center for Cancer Prevention and Drug Development, Department of Medicine, Hem-Onc Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Coastside Bio Resources, Deer Isle, Maine.
Cancer Prev Res (Phila). 2015 Apr;8(4):327-37. doi: 10.1158/1940-6207.CAPR-14-0380. Epub 2015 Feb 5.
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.
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能够增强先天免疫反应并抑制APC(Min/+)小鼠的肠道肿瘤。在评估肠道肿瘤抑制作用之前，将APC(Min/+)小鼠喂食含0、250或500 ppm Frondanol A5的半纯化饮食14周。膳食中的Frondanol A5可使雄性小鼠小肠息肉大小和形成减少高达30%（P < 0.02），雌性小鼠减少高达50%（P < 0.01）。重要的是，与未处理的雄性APC(Min/+)小鼠相比，250 ppm和500 ppm Frondanol A5饮食可使结肠肿瘤数量分别减少65%（P < 0.007）和75%（P < 0.0001）。在雌性APC(Min/+)小鼠中，两种剂量水平的Frondanol A5均可使结肠肿瘤数量减少高达80%（P < 0.0001）。从处理过的小鼠中分离出的腹腔巨噬细胞显示吞噬效率增加（对照组为24%，处理组为50%；P < 0.01），并且GILT mRNA表达增加，表明处理过的动物体内这些细胞的先天免疫反应增强。同样，与未处理的肿瘤相比，我们观察到处理过的肿瘤中GILT表达增加。此外，在治疗组中观察到G-CSF细胞因子增加，炎症细胞因子和标志物5-LOX、其调节剂FLAP、增殖（PCNA）和血管生成（VEGF）标志物减少。这些数据表明，Frondanol A5可降低炎症血管生成分子，增加GILT表达和巨噬细胞吞噬作用。这些降低可能改善了处理过的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对肠道肿瘤发生具有显著的化学预防潜力。
