TY - JOUR T1 - Mcl-1 Blocks Radiation-induced Apoptosis and Inhibits Clonogenic Cell Death JF - Anticancer Research JO - Anticancer Res SP - 2697 LP - 2703 VL - 25 IS - 4 AU - HANS SKVARA AU - CHRISTIANE THALLINGER AU - VOLKER WACHECK AU - BRETT P. MONIA AU - HUBERT PEHAMBERGER AU - BURKHARD JANSEN AU - EDGAR SELZER Y1 - 2005/07/01 UR - http://ar.iiarjournals.org/content/25/4/2697.abstract N2 - Background: Anti-apoptotic Bcl-2 family proteins, such as Bcl-2 and Bcl-x, can modulate radio- and/or chemosensitivity of human malignancies. Since no information is available on the role Mcl-1 may play in the radioresponse of tumor cells, the relationship between Mcl-1 expression and response to ionizing radiation (IR) was investigated using an antisense strategy. Materials and Methods: Human melanoma cells were treated with Mcl-1 antisense oligonucleotides (ASOs) and IR. The effects of antisense treatment alone or in combination with IR on proliferation, induction of apoptosis and clonogenic cell death were evaluated. Results: ASO treatment in combination with IR reduced the mean cell numbers 9.5-fold compared to a 2.6-fold reduction after ASO treatment alone and a 1.6-fold reduction after IR alone. The percentages of apoptosis measured (means±SD) were 49%±3.0 in antisense/IR-treated cultures compared to 1.3%±0.5, 14.3%±0.5, 7.3%±1.1 and 10.3%±0.6 in ASO controls, in antisense-treated, in IR-treated and in antisense control plus IR-treated cells, respectively. Colony formation assays demonstrated a synergistic effect of Mcl-1 down-regulation with IR. Conclusion: Mcl-1 expression affects the radioresistance of human melanoma cells. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -