Isoliquiritigenin inhibits migration and invasion of prostate cancer cells: possible mediation by decreased JNK/AP-1 signaling
Isoliquiritigenin inhibits migration and invasion of prostate cancer cells: possible mediation by decreased JNK/AP-1 signaling
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DOI：
10.1016/j.jnutbio.2008.06.005
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发表时间：
2009-09-01
影响因子：
5.6
通讯作者：
Park, Jung Han Yoon
中科院分区：
文献类型：
--
作者：
Kwon, Gyoo Taik;Cho, Han Jin;Park, Jung Han Yoon
异甘草素(ISL，4，2‘，4’-三羟基查尔酮)广泛存在于甘草、葱和豆芽中，是一种具有抗炎和抗癌作用的强效抗氧化剂。本研究旨在探讨ISL对人前列腺癌DU-145细胞迁移、侵袭和黏附特性的影响。DU145细胞在0~20mU/L的L溶液中培养，加或不加10mU/L表皮生长因子。ISL可剂量依赖性地抑制基础和EGF诱导的细胞迁移、侵袭和黏附。ISL抑制EGF诱导的尿激酶型纤溶酶原激活物(UPA)、基质金属蛋白酶(MMP)-9的分泌。组织金属蛋白酶抑制因子-1(TIMP-1)和血管内皮生长因子(VEGF)，但以浓度依赖方式增加TIMP-2的分泌。降低整合素α2、细胞间黏附分子和血管细胞黏附分子的蛋白水平以及uPA、MMP9、血管内皮生长因子、细胞间黏附分子和整合素α2mRNA的表达水平。此外，基础激活蛋白和表皮生长因子诱导的激活蛋白-L结合活性和Jun氨基末端激酶、C-jun和Akt的磷酸化水平也降低。然而，细胞外信号调节蛋白激酶(ERK)1/2和p38丝裂原活化蛋白激酶的磷酸化没有改变。JNK抑制剂SP600125抑制基础和EGF诱导的uPA、VEGF、MMP9和TIMP-1的分泌，并抑制AM DNA结合活性和细胞迁移。这些结果为ISL作为一种有效的抗转移剂的作用提供了证据，它可以显著抑制前列腺癌的转移和侵袭能力。抑制JNK/AP-1信号转导可能是ISL抑制癌细胞侵袭和迁移的机制之一。(C)2009 Elsevier Inc.保留所有权利。
Isoliquiritigenin (ISL, 4,2',4'-trihydroxychalcone), which is found in licorice, shallot and bean sprouts, is a potent antioxidant with anti-inflammatory and anti-carcinogenic effects. The purpose of this Study was to investigate the effects of ISL treatment on the migration, invasion and adhesion characteristics of DU 145 human prostate cancer cells. DU 145 cells were Cultured in the presence of 0-20 mu mol/L ISL with or without 10 mu g/L epidermal growth factor (EGF). ISL inhibited basal and EGF-induced cell migration, invasion and adhesion dose dependently. ISL decreased EGF-induced secretion of urokinase-type plasminogen activator (uPA), matrix metalloproteinase (MMP)-9. tissue inhibitor of metalloprotemase-1 (TIMP-1), and vascular endothelial growth factor (VEGF), but increased TIMP-2 secretion in a concentration-dependent manner. In addition, ISL decreased the protein levels of integrin-alpha 2, intercellular adhesion molecular (ICAM) and vascular cell adhesion molecule (VCAM), and mRNA levels of uPA, MMP-9, VEGF, ICAM and integrin-alpha 2. Furthermore, basal and EGF-induced activator protein (AP)-l binding activity and phosphorylation Of Jun N-terminal kinase (JNK), C-Jun and Akt were decreased after ISL treatment. However, phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase was not altered. The JNK inhibitor SP600125 inhibited basal and EGF-induced secretion of uPA, VEGF, MMP-9 and TIMP-1, as well as AM DNA binding activity and cell migration. These results provide evidence for the role of ISL as a potent antimetastatic agent, which can markedly inhibit the metastatic and invasive capacity of prostate cancer cells. The inhibition of JNK/AP-1 signaling may be one of the mechanisms by which ISL inhibits cancer cell invasion and migration. (C) 2009 Elsevier Inc. All rights reserved.