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

  • Authors:
    • Patrizia Portanova
    • Tiziana Russo
    • Ornella Pellerito
    • Giuseppe Calvaruso
    • Michela Giuliano
    • Renza Vento
    • Giovanni Tesoriere
  • View Affiliations

  • Published online on: August 1, 2008     https://doi.org/10.3892/ijo_00000012
  • Pages: 325-331
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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.

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August 2008
Volume 33 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Portanova P, Russo T, Pellerito O, Calvaruso G, Giuliano M, Vento R and Tesoriere G: The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma HT-29 cells. Int J Oncol 33: 325-331, 2008
APA
Portanova, P., Russo, T., Pellerito, O., Calvaruso, G., Giuliano, M., Vento, R., & Tesoriere, G. (2008). The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma HT-29 cells. International Journal of Oncology, 33, 325-331. https://doi.org/10.3892/ijo_00000012
MLA
Portanova, P., Russo, T., Pellerito, O., Calvaruso, G., Giuliano, M., Vento, R., Tesoriere, G."The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma HT-29 cells". International Journal of Oncology 33.2 (2008): 325-331.
Chicago
Portanova, P., Russo, T., Pellerito, O., Calvaruso, G., Giuliano, M., Vento, R., Tesoriere, G."The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma HT-29 cells". International Journal of Oncology 33, no. 2 (2008): 325-331. https://doi.org/10.3892/ijo_00000012