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.

CARLISI, D., LAURICELLA, M., D'ANNEO, A., EMANUELE, S., ANGILERI, L., DI FAZIO, P., et al. (2009). The histone deacetylase inhibitor suberoylanilide hydroxamic acid sensitizes human hepatocellular carcinoma cells to TRAIL-induced apoptosis by TRAIL-DISC activation. EUROPEAN JOURNAL OF CANCER, 45(13), 2425-2438 [10.1016/j.ejca.2009.06.024].

The histone deacetylase inhibitor suberoylanilide hydroxamic acid sensitizes human hepatocellular carcinoma cells to TRAIL-induced apoptosis by TRAIL-DISC activation

CARLISI, Daniela;LAURICELLA, Marianna;D'ANNEO, Antonella;EMANUELE, Sonia;ANGILERI, Liliana;DI FAZIO, Pietro;SANTULLI, Andrea;VENTO, Renza;TESORIERE, Giovanni
2009

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.
Settore BIO/10 - Biochimica
CARLISI, D., LAURICELLA, M., D'ANNEO, A., EMANUELE, S., ANGILERI, L., DI FAZIO, P., et al. (2009). The histone deacetylase inhibitor suberoylanilide hydroxamic acid sensitizes human hepatocellular carcinoma cells to TRAIL-induced apoptosis by TRAIL-DISC activation. EUROPEAN JOURNAL OF CANCER, 45(13), 2425-2438 [10.1016/j.ejca.2009.06.024].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/47857
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