Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell response to histone deacetylase inhibitor
Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell response to histone deacetylase inhibitor
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DOI：
10.1073/pnas.0607518103
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发表时间：
2006-10-17
影响因子：
11.1
通讯作者：
Marks, Paul A.
中科院分区：
文献类型：
--
作者：
Xu, Weisheng;Ngo, Lang;Marks, Paul A.
因此，迫切需要开发更好的基于机制的前列腺癌治疗方法。在这项调查中，我们研究了四个人前列腺癌细胞系，LNCaP，DU 145，LAPC 4和PC 3，这四个细胞系对组蛋白去乙酰化酶抑制剂辛二酰苯胺异羟肟酸（伏立诺他）的反应不同，这是一种新的抗癌药物。检查内在的线粒体半胱天冬酶依赖性细胞凋亡和半胱天冬酶独立的，活性氧（ROS）促进细胞死亡的作用，提供了一个机制，可能会决定不同的响应组蛋白去乙酰化酶抑制剂的理解。我们发现这些癌细胞在组成性表达和对辛二酰苯胺异羟肟酸的反应中存在显著差异，包括抗凋亡和促凋亡蛋白水平、线粒体膜完整性、半胱天冬酶激活、ROS积累和硫氧还蛋白（ROS的主要清除剂）表达。鉴定这些差异可以在评估治疗反应和鉴定靶点以增强治疗功效方面具有预测价值。
There is a great need to develop better mechanism-based therapies for prostate cancer. In this investigation, we studied four human prostate cancer cell lines, LNCaP, DU145, LAPC4, and PC3, which differ in response to the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (vorinostat), a new anticancer drug. Examining the role of intrinsic mitochondrial caspase-dependent apoptosis and caspase-independent, reactive oxygen species (ROS) facilitated cell death, has provided an understanding of mechanisms that may determine the varied response to the histone deacetylase inhibitor. We found striking differences among these cancer cells in constitutive expression and response to suberoylanilide hydroxamic acid in levels of antiapoptotic and proapoptotic proteins, mitochondria membrane integrity, activation of caspases, ROS accumulation, and expression of thioredoxin, the major scavenger of ROS. Identifying these differences can have predictive value in assessing therapeutic response and identifying targets to enhance therapeutic efficacy.