Trichostatin A - histone deacetylase inhibitor with clinical therapeutic potential - is also a selective and potent inhibitor of gelatinase A expression
Trichostatin A - histone deacetylase inhibitor with clinical therapeutic potential - is also a selective and potent inhibitor of gelatinase A expression
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DOI：
10.1016/s0006-291x(02)02420-8
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发表时间：
2002-10-18
影响因子：
3.1
通讯作者：
Silverman, M
中科院分区：
文献类型：
--
作者：
Ailenberg, M;Silverman, M
目前正在探索组蛋白乙酰化的调控作为癌症治疗的一种治疗策略。具体地说，曲古菌素A(TSA)对历史性脱乙酰酶的抑制已被证明可以防止肿瘤的发生和转移。在这篇论文中，我们证明了TSA处理的3T3细胞历史上增加的乙酰化降低了明胶酶A的mRNA和酶谱活性，明胶酶A是一种基质金属蛋白酶，其本身与肿瘤的发生和转移有关。此外，TSA抑制细胞松弛素D诱导的明胶酶A的激活，但不影响明胶酶A激活复合体的其他成员MT1-MMPs和TIMP-2。因此，TSA是明胶酶A表达和激活的选择性和有效的抑制剂。这一发现不仅加强了继续研究TSA在癌症中的治疗作用的理论基础，而且也为TSA抑制明胶酶A的表达和激活提供了证据，可以作为监测和确定涉及TSA的临床试验的终点的生物标志物。(C)2002年埃尔塞维尔科学公司(美国)。版权所有。
Modulation of histone acetylation is currently being explored as a therapeutic strategy in treatment of cancer. Specifically, inhibition of historic deacetylase by trichostatin A (TSA) has been shown to prevent tumorigenesis and metastasis. In the present paper we demonstrate that increased historic acetylation by TSA-treated 3T3 cells decreases mRNA as well as zymographic activity of gelatinase A, a matrix metalloproteinase, which is itself, implicated in tumorigenesis and metastasis. Furthermore, TSA inhibits cytochalasin D-induced activation of gelatinase A, but TSA does not affect other members of the gelatinase A activation complex, MT1-MMP and TIMP-2. Thus, TSA is a selective and potent inhibitor of expression and activation of gelatinase A. This finding not only strengthens the rationale for continuing to investigate the therapeutic utility of TSA in cancer, but also, provides evidence that TSA inhibition of gelatinase A expression and activation can be used as a biological marker to monitor and determine end-points of clinical trials involving TSA. (C) 2002 Elsevier Science (USA). All rights reserved.