CDDO induces apoptosis via the intrinsic pathway in lymphoid cells

S. Inoue, R. T. Snowden, M. J.S. Dyer, G. M. Cohen

研究成果: Article査読

55 被引用数 (Scopus)

抄録

The peroxisome-proliferator-activated receptor (PPAR) γ agonist, CDDO, is under investigation for use in various malignancies. The mechanisms by which CDDO induces apoptosis are controversial. We have therefore sought to determine these mechanisms using primary chronic lymphocyte leukemic (CLL) cells and Jurkat cell lines with defined apoptotic abnormalities. In these cells, CDDO induced-apoptosis involved caspase-independent loss in mitochondrial membrane potential followed by caspase processing. The pattern of CDDO-induced caspase processing, defined by use of a caspase inhibitor, strongly suggested that caspase-9 was the apical caspase. Moreover, CDDO induced apoptosis in caspase-8 and FADD-deficient but not in Bcl-xL overexpressing Jurkat cells. In CLL cells, CDDO induced an early release of mitochondrial cytochrome c and Smac that preceded apoptosis. Thus, in both cell types, CDDO induced apoptosis primarily by the intrinsic pathway with caspase-9 as the apical caspase. This has important implications in the design of novel agents for the treatment of CLL and other malignancies.

本文言語English
ページ(範囲)948-952
ページ数5
ジャーナルLeukemia
18
5
DOI
出版ステータスPublished - 2004 5月
外部発表はい

ASJC Scopus subject areas

  • 血液学
  • 腫瘍学
  • 癌研究

フィンガープリント

「CDDO induces apoptosis via the intrinsic pathway in lymphoid cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル