Enterolactone inhibits insulin-like growth factor-1 receptor signaling in human prostatic carcinoma PC-3 cells.
Enterolactone inhibits insulin-like growth factor-1 receptor signaling in human prostatic carcinoma PC-3 cells.
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DOI：
10.3945/jn.108.101832
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Chen LH;Fang J;Sun Z;Li H;Wu Y;Demark-Wahnefried W;Lin X
肠内酯是植物木脂素的主要代谢产物，已被证明可抑制前列腺癌的生长和发展，但其抗癌活性的机制基础在很大程度上仍然未知。胰岛素样生长因子-1受体（IGF-1 R）信号的激活对前列腺癌细胞的生长和进展至关重要。本研究探讨肠内酯的生长抑制作用是否与PC-3前列腺癌细胞中IGF-1/IGF-1 R系统的变化有关。在营养相关浓度（20-60 μmol/L），肠内酯抑制IGF-1诱导的IGF-1 R及其下游AKT和丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）信号通路的激活。肠内酯对AKT的抑制导致其下游靶点磷酸化水平降低，包括p70 S6 K1和糖原合成酶激酶-3 β（GSK-3 β）。肠内酯还抑制细胞周期蛋白D1的表达。结果，肠内酯抑制PC-3细胞的增殖和迁移。通过si-RNA敲低IGF-1 R导致PC-3细胞的增殖抑制，并且当si-IGF-1 R组（用含有针对IGF-1 R mRNA的siRNA的质粒转染的细胞）用或不用肠内酯处理时，未观察到细胞数量的显著差异。这些结果表明，肠内酯抑制前列腺癌细胞的增殖和迁移，至少部分，通过抑制IGF-1/IGF-1 R信号。这项研究的发现为肠内酯对前列腺癌的分子机制提供了新的见解。
Enterolactone, a major metabolite of plant-based lignans, has been shown to inhibit prostate cancer growth and development, but the mechanistic basis for its anticancer activity remains largely unknown. Activation of insulin-like growth factor-1 receptor (IGF-1R) signaling is critical for prostate cancer cell growth and progression. The present study examined whether the growth inhibitory effect of enterolactone was related to changes in the IGF-1/IGF-1R system in PC-3 prostate cancer cells. At nutritionally relevant concentrations (20-60 μmol/L), enterolactone inhibited IGF-1-induced activation of IGF-1R and its downstream AKT and mitogen-activated protein kinase (MAPK)/extracellular-signal regulated kinase (ERK) signaling pathways. Inhibition of AKT by enterolactone resulted in decreased phosphorylation of its downstream targets, including p70S6K1 and glycogen synthase kinase-3 beta (GSK-3 β). Enterolactone also inhibited cyclin D1 expression. As a result, enterolactone inhibited proliferation and migration of PC-3 cells. Knockdown of IGF-1R by si-RNA resulted in inhibition of proliferation of PC-3 cells and no significant differences in the cell numbers were observed when the si-IGF-1R groups (cells transfected with plasmaids containing siRNA against IGF-1R mRNA) were treated with or without enterolactone. These results suggest that enterolactone suppresses proliferation and migration of prostate cancer cells, at least partially, through inhibition of IGF-1/IGF-1R signaling. The finding of this study provides new insights into the molecular mechanisms that enterolactone exerts against prostate cancer.
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影响因子：
6.4
作者：
BRESLOW, N;CHAN, CW;TULINIUS, H
通讯作者：
TULINIUS, H
DOI：
10.1158/1055-9965.epi-08-0008
发表时间：
2008-12
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Demark-Wahnefried W;Polascik TJ;George SL;Switzer BR;Madden JF;Ruffin MT 4th;Snyder DC;Owzar K;Hars V;Albala DM;Walther PJ;Robertson CN;Moul JW;Dunn BK;Brenner D;Minasian L;Stella P;Vollmer RT
通讯作者：
Vollmer RT
影响因子：
5.7
作者：
Chen, Li-Hua;Fang, Jing;Lin, Xu
通讯作者：
Lin, Xu
影响因子：
1.4
作者：
Baserga, R
通讯作者：
Baserga, R
影响因子：
2.1
作者：
Demark-Wahnefried, W;Price, DT;Vollmer, RT
通讯作者：
Vollmer, RT