The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma HT-29 cells.

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Histone deacetylase inhibitors (HDACIs) activate genes that promote cell cycle arrest and apoptosis in a number of tumor cells. This study showed that suberoylanilide hydroxamic acid (SAHA), a potent and commonly used HDACI, induced apoptosis in human colon adenocarcinoma HT-29 cells in a time- and dose-dependent manner. This effect was accompanied by the induction of oxidative stress, dissipation of mitochondrial transmembrane potential and activation of executioner caspases. Moreover, SAHA increased the levels of phosphorylated active forms of p38 and JNK. The addition of either the antioxidant N-acetylcysteine or the specific inhibitor of NADPH oxidase diphenylene iodonium chloride reduced the cytotoxic effects of SAHA in HT-29 cells, suggesting that the induction of oxidative stress represents a crucial event in the apoptotic mechanism. In addition, SAHA up-regulated the death receptor DR5, inducing the activation of caspase-8 with the consequent cleavage of Bid. Furthermore, SAHA down-regulated FLIPL and Akt, two proteins which exert an inhibitory role in apoptosis.
Original languageEnglish
Pages (from-to)325-331
Number of pages7
JournalInternational Journal of Oncology
Volume33
Publication statusPublished - 2008

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma HT-29 cells.'. Together they form a unique fingerprint.

Cite this