Department of Medicine, University of Oklahoma Cancer Institute, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, USA.
Cancer Prev Res (Phila). 2010 Jan;3(1):82-91. doi: 10.1158/1940-6207.CAPR-09-0112.
Sea cucumber extracts have been widely used to treat individuals with inflammatory conditions in East Asia. The present study has been designed to test potential colon cancer-preventive properties of Frondanol A5, a glycolipid extract from the sea cucumber, Cucumaria frondosa, using in vivo and in vitro models of colon cancer. Chemopreventive efficacy of Frondanol A5 was evaluated on azoxymethane-induced rat colon carcinogenesis using colonic aberrant crypt foci (ACF) as efficacy marker. At 7 weeks of age, groups of rats (12 per group) were fed the AIN-76A diet, and ACFs were induced by azoxymethane (15 mg/kg body weight). Three days after azoxymethane treatment, rats were fed with the diets containing 0, 150, and 450 ppm of Frondanol A5 and continued on the diets for 8 weeks, at which time ACFs were evaluated. Expression levels of proliferating cell nuclear antigen and p21(WAF1/CIP1) were determined in ACFs. Further, Frondanol A5 (10-120 microg/mL) was studied for its growth-inhibitory and apoptotic effects in the HCT-116 cell line. Dietary administration of 150 and 450 ppm of Frondanol A5 significantly suppressed azoxymethane-induced total colonic ACF formation, approximately 34% to 55% (P < 0.01 to P < 0.0001), and multicrypt aberrant foci (48-68.5%, P < 0.0001) in a dose-dependent manner. ACFs in rats treated with Frondanol A5 showed significant upregulation of p21(WAF1/CIP1) and downregulation of proliferating cell nuclear antigen compared with control group. Frondanol A5 showed growth inhibition at S and G(2)-M phase with a decrease in Cdc25c and an increase in p21(WAF1/CIP) with significant apoptosis associated with H2AX phosphorylation and caspase-2 cleavage in HCT116 cells. Overall, Frondanol A5 exhibits potential chemopreventive properties for colon carcinogenesis, which suggests further development of this sea cucumber extract.
海参提取物在东亚被广泛用于治疗炎症患者。本研究旨在通过体内和体外结肠癌模型测试 Frondanol A5（一种来自海参 Cucumaria frondosa 的糖脂提取物）预防结肠癌的潜在特性。Frondanol A5 的化学预防效果通过结肠异常隐窝病灶（ACF）作为疗效标志物在氧化偶氮甲烷诱导的大鼠结肠癌发生中进行评估。在 7 周龄时，将大鼠（每组 12 只）用 AIN-76A 饮食喂养，并通过氧化偶氮甲烷（15 mg/kg 体重）诱导 ACF。氧化偶氮甲烷处理后 3 天，用含有 0、150 和 450 ppm Frondanol A5 的饮食喂养大鼠，并继续喂养 8 周，此时评估 ACF。在 ACF 中测定增殖细胞核抗原和 p21（WAF1/CIP1）的表达水平。进一步研究了 Frondanol A5（10-120μg/mL）对 HCT-116 细胞系的生长抑制和凋亡作用。饮食中添加 150 和 450 ppm Frondanol A5 可显著抑制氧化偶氮甲烷诱导的总结肠 ACF 形成，约 34%至 55%（P < 0.01 至 P < 0.0001），多隐窝异常病灶（48-68.5%，P < 0.0001）呈剂量依赖性。与对照组相比，Frondanol A5 处理的大鼠的 ACF 中 p21（WAF1/CIP1）表达显著上调，增殖细胞核抗原表达下调。Frondanol A5 在 S 和 G(2)-M 期表现出生长抑制，Cdc25c 减少，p21（WAF1/CIP1）增加，与 H2AX 磷酸化和 caspase-2 切割相关的显著凋亡与 HCT116 细胞。总的来说，Frondanol A5 对结肠癌发生具有潜在的化学预防特性，这表明这种海参提取物的进一步开发。
