The histone deacetylase inhibitor, suberoylanilide hydroxamic acid, overcomes resistance of human breast cancer cells to Apo2L/TRAIL

摘要: While the apoptosis-inducing ligand Apo2L/TRAIL is a promising new agent for treatment of cancer, sensitivity cancer cells induction apoptosis by varies considerably. Identification agents that can be used in combination with to enhance breast would increase potential utility this as therapeutic. Here, we show histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), sensitize Apo2L/TRAIL-resistant Apo2L/TRAIL-induced apoptosis. Importantly, neither alone, nor SAHA, affected viability normal human culture. MDA-MB-231 cells, generated long-term culture continuous presence Apo2L/TRAIL, were resensitized SAHA. The sensitization these SAHA was accompanied activation caspase 8, 9 and 3 concomitant Bid PARP cleavage. expression proapoptotic protein, Bax, increased significantly high levels Bax maintained combined Apo2L/TRAIL. Treatment cell surface DR5 but not DR4. Interestingly, also resulted significant DcR1. Taken together, our findings indicate use 2 may effective cancer. © 2006 Wiley-Liss, Inc.