Hinokitiol, a metal chelator derived from natural plants, suppresses cell growth and disrupts androgen receptor signaling in prostate carcinoma cell lines
Hinokitiol, a metal chelator derived from natural plants, suppresses cell growth and disrupts androgen receptor signaling in prostate carcinoma cell lines
复制标题
DOI：
10.1016/j.bbrc.2006.09.166
复制
发表时间：
2006-12-08
影响因子：
3.1
通讯作者：
Yamauchi, Hitoshi
中科院分区：
文献类型：
--
作者：
Liu, Shicheng;Yamauchi, Hitoshi
扁柏酚（β-崖柏素）是一种在柏科植物心材中发现的与托洛酮相关的化合物，它能强烈抑制多种肿瘤细胞系的增殖。这是第一份证明扁柏酚，一种来自天然植物的金属螯合剂，抑制前列腺癌细胞系中的细胞生长并破坏AR信号的报告。我们目前的研究表明，扁柏酚抑制雄激素/AR介导的细胞生长和雄激素刺激的DNA合成的[H-3]胸苷掺入的剂量和时间依赖性的方式。扁柏酚同时抑制细胞内和分泌的PSA水平，这是前列腺癌进展的标志物。扁柏酚以剂量和时间依赖性方式显著抑制AR mRNA和蛋白表达。此外，配体结合试验表明，扁柏酚阻断合成雄激素[H-3]R1881与LNCaP细胞中AR的结合。这些研究结果共同表明，扁柏酚是潜在的有效抗前列腺癌在体外，因此，它可能成为一种新的化学预防或化疗剂前列腺癌。(c)2006年爱思唯尔公司All rights reserved.
Hinokitiol (beta-thujaplicin), a troplone-related compound found in the heartwood of cupressaceous plants, strongly inhibits the proliferation of a broad range of tumor cell lines. This is the first report to demonstrate that hinokitiol, a metal chelator derived from natural plants, suppresses cell growth and disrupts AR signaling in prostate carcinoma cell lines. Our present studies indicate that hinokitiol suppresses androgen/AR-mediated cell growth and androgen-stimulated DNA synthesis by [H-3]thymidine incorporation in a dose- and time-dependent manner. Hinokitiol simultaneously suppresses the intracellular and secreted PSA levels, a marker for the progression of prostate cancer. Hinokitiol significantly represses the AR mRNA and protein expression in a dose- and time-dependent manner. Additionally, the ligand-binding assay shows that hinokitiol blocks binding of the synthetic androgen [H-3]R1881 to AR in LNCaP cells. These findings collectively suggest that hinokitiol is potentially effective against prostate cancer in vitro, and thus it might become a novel chemopreventive or chemotherapeutic agent for prostate cancer. (c) 2006 Elsevier Inc. All rights reserved.