Anti-Pancreatic Cancer Effects of a Polar Extract From the Edible Sea Cucumber, Cucumaria frondosa
Anti-Pancreatic Cancer Effects of a Polar Extract From the Edible Sea Cucumber, Cucumaria frondosa
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DOI：
10.1097/mpa.0b013e3181c72baf
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发表时间：
2010-07-01
期刊：
影响因子：
2.9
通讯作者：
Adrian, Thomas E.
中科院分区：
文献类型：
--
作者：
Roginsky, Alexandra B.;Ding, Xian-Zhong;Adrian, Thomas E.
目的：目的：探讨佛丹酚-A5 P对人胰腺癌细胞S2013和AsPC-1的生长抑制和凋亡作用及其机制。方法：观察佛丹酚-A5 P对人胰腺癌细胞S2013和AsPC-1增殖、细胞周期、细胞周期蛋白和p21（waf 1）表达、MAP激酶磷酸化、膜联蛋白V结合和caspase-3激活的影响。Frondanol-A5 P抑制两种细胞系的增殖并诱导G（2）/M期细胞周期停滞，同时降低细胞周期蛋白A、细胞周期蛋白B和cdc 25 c的表达。Frondanol-A5 P在5分钟内诱导应激活化蛋白激酶和Janus激酶（SAPK/JAK）以及p38丝裂原活化蛋白激酶（MAP）的磷酸化。在3小时，Frondanol-A5 P显著增加两种细胞系中p21（waf 1）信使RNA和蛋白的表达。p38激酶抑制剂SB 203580可降低这种作用。Frondanol-A5 P可显著增加胰腺癌细胞膜联蛋白V结合，激活caspase-3。结论：Frondanol-A5可诱导胰腺癌细胞周期阻滞和凋亡。这些变化与细胞周期蛋白A、细胞周期蛋白B和cdc 25 c的表达减少以及p21（waf 1）的表达增加有关，至少部分是由p38激酶依赖性机制介导的。由于Frondanol-A5 P来源于可食用的无毒海参，因此它可能对营养治疗或预防胰腺癌有价值。
Objectives: To investigate the effects and mechanism of Frondanol-A5P, a polar extract from Cucumaria frondosa, on growth inhibition and apoptosis in S2013 and AsPC-1 human pancreatic cancer cells.Methods: The effects of Frondanol-A5P on proliferation, cell cycle, expression of cell cycle proteins and p21(waf1), phosphorylation of MAP kinases, annexin V binding, and caspase-3 activation were examined.Results: Frondanol-A5P inhibited proliferation and induced G(2)/M phase cell cycle arrest in both cell lines with decreased expression of cyclin A, cyclin B, and cdc25c. Frondanol-A5P induced phosphorylation of stress-activated protein kinase and Janus kinase (SAPK/JAK) and p38 mitogen-activated protein kinase (MAP) within 5 minutes. Frondanol-A5P markedly increased expression of p21(waf1) messenger RNA and protein at 3 hours in both cell lines. This effect was reduced by the p38 kinase inhibitor, SB203580. Frondanol-A5P markedly increased annexin V binding and activated caspase-3.Conclusions: Frondanol-A5 causes cell cycle arrest and apoptosis in human pancreatic cancer cells. These changes are associated with decreased expression of cyclin A, cyclin B, and cdc25c and increased expression of p21(waf1) that, at least in part, is mediated by a p38 kinase-dependent mechanism. Because Frondanol-A5P is derived from an edible, nontoxic, sea cucumber, it may be valuable for nutritional therapy or prevention of pancreatic cancer.