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The histone deacetylase inhibitor suberoylanilide hydroxamic acid sensitises human hepatocellular carcinoma cells to TRAIL-induced apoptosis by TRAIL-DISC activation
- Source :
-
European Journal of Cancer . Sep2009, Vol. 45 Issue 13, p2425-2438. 14p. - Publication Year :
- 2009
-
Abstract
- Abstract: This paper shows that the histone deacetylase inhibitor SAHA sensitised at sub-toxic doses human hepatocellular carcinoma cells (HepG2, Hep3B and SK-Hep1) to TRAIL-induced apoptosis, while it was ineffective in primary human hepatocytes (PHHs). In particular in HCC cells SAHA increased the expression of death receptor 5 (DR5) and caused a decrement of c-Flip. These two modifications provoked in the presence of TRAIL the rapid production of TRAIL-DISC and the activation of caspase-8. Consequently SAHA/TRAIL combination induced many apoptotic events, such as a cleavage of Bid into tBid, dissipation of mitochondrial membrane potential, activation of caspase-3 with the consequent cleavage of both NF-kB and Akt. The decrease in NF-kB level seemed to be responsible for the reduction in the content of IAP family antiapoptotic proteins while the decrease in Akt level caused a reduction in phospho-Bad. These events led to the activation of caspase-9, which contributed to the strong apoptotic activity of TRAIL. Sensitisation of human hepatocellular carcinoma cells to TRAIL-induced apoptosis by SAHA may suggest new strategies for the treatment of liver tumours. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 09598049
- Volume :
- 45
- Issue :
- 13
- Database :
- Academic Search Index
- Journal :
- European Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 43871665
- Full Text :
- https://doi.org/10.1016/j.ejca.2009.06.024