Mcl-1 Blocks Radiation-induced Apoptosis and Inhibits Clonogenic Cell Death

• Published in: Anticancer research Vol. 25; no. 4; pp. 2697 - 2703
• Main Authors: SKVARA, Hans, THALLINGER, Christiane, WACHECK, Volker, MONIA, Brett P, PEHAMBERGER, Hubert, JANSEN, Burkhard, SELZER, Edgar
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-07-2005
• Subjects: Apoptosis - genetics; Apoptosis - radiation effects; Biological and medical sciences; Cell Death - genetics; Cell Death - radiation effects; Cell Line, Tumor; Dermatology; Humans; Medical sciences; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Melanoma - radiotherapy; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Oligonucleotides, Antisense - genetics; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - genetics; Radiation Tolerance; Transfection; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Bcl-2; Protein MCL-1; Antisense oligonucleotides; melanoma; Malignant tumor; Antisense oligonucleotide; Mcl-1; Ionizing radiation; Cancerology; Cell death; C-Onc gene; Malignant melanoma; Inhibitor; Protooncogene; Apoptosis
• ISSN: 0250-7005; 1791-7530

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.