• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pigment cell research >Melanoma cell lines are susceptible to histone deacetylase inhibitor TSA provoked cell cycle arrest and apoptosis
【24h】

Melanoma cell lines are susceptible to histone deacetylase inhibitor TSA provoked cell cycle arrest and apoptosis

机译：黑色素瘤细胞系易受组蛋白脱乙酰基酶抑制剂TSA的刺激而导致细胞周期停滞和凋亡

获取原文
获取原文并翻译 | 示例
       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Melanoma is the most aggressive of skin cancers because of its high resistance to currently available therapy. Although melanoma cells often retain wild-type p53 tumour suppressor protein and express it at high levels, the p53 mediated apoptosis pathway is suppressed. Histone deacetylase (HDAC) inhibitors are a promising group of compounds inducing differentiation, growth arrest and apoptosis in tumour cells in preclinical studies. We have studied the cellular effects of trichostatin A (TSA), a HDAC inhibitor, in a panel of melanoma cell lines and its mechanism of action in relation to p53. TSA stabilized wild-type p53, but p53 protein accumulation was overridden by simultaneous downregulation of p53 mRNA leading to a decrease in p53 protein. While growth arrest was induced in all cell lines studied and apoptosis in most (6/7), these cellular effects were independent of the p53 status of the cells. Inhibiting p53 function by a dominant negative p53 (p53(175His)) confirmed that the HDAC inhibitor induced apoptosis was independent of wild-type p53, even though TSA slightly activated p53 in a reporter assay. The results indicate that while the action of TSA is independent of p53, the activation of the apoptosis pathway by the HDAC inhibitors may provide therapeutic approaches for melanoma treatment.
机译：黑色素瘤是皮肤癌中最具有侵略性的，因为它对目前可用的疗法具有很高的抵抗力。尽管黑素瘤细胞通常保留野生型p53肿瘤抑制蛋白并高水平表达，但p53介导的凋亡途径却被抑制。在临床前研究中，组蛋白脱乙酰基酶（HDAC）抑制剂是一组在肿瘤细胞中诱导分化，生长停滞和凋亡的有前途的化合物。我们已经研究了HDAC抑制剂曲古抑菌素A（TSA）在一组黑色素瘤细胞系中的细胞效应及其相对于p53的作用机理。 TSA稳定了野生型p53，但p53蛋白同时下调导致p53蛋白减少，从而使p53蛋白积累被覆盖。尽管在所有研究的细胞系中都诱导了生长停滞，而大多数细胞系中却诱导了细胞凋亡（6/7），但这些细胞效应与细胞的p53状态无关。通过显性阴性p53（p53（175His））抑制p53功能，证实了HDAC抑制剂诱导的凋亡独立于野生型p53，尽管在报告基因分析中TSA稍微激活了p53。结果表明，虽然TSA的作用不依赖于p53，但HDAC抑制剂对细胞凋亡途径的激活可能为黑素瘤治疗提供治疗方法。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号