Didox (A Novel Ribonucleotide Reductase Inhibitor) Overcomes bcl-2 Mediated Radiation Resistance in Prostate Cancer Cell Line PC-3

• Published in: Cancer biology & therapy Vol. 1; no. 5; pp. 539 - 545
• Main Authors: Inayat, Mohammed S., Chendil, Damodaran, Mohiuddin, Mohammed, Elford, Howard L., Gallicchio, Vincent S., Ahmed, Mansoor M.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.09.2002
• Subjects: Antineoplastic Agents - therapeutic use; Apoptosis - radiation effects; bcl-2-Associated X Protein; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cell Line; Cell Survival - radiation effects; Combined Modality Therapy; Cycle; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Gene Expression Regulation, Neoplastic - radiation effects; Genetic Vectors; Humans; Hydroxamic Acids - therapeutic use; Landes; Male; Mitosis - drug effects; Mitosis - radiation effects; NF-kappa B - drug effects; NF-kappa B - radiation effects; Organogenesis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - radiotherapy; Proteins; Proto-Oncogene Proteins - drug effects; Proto-Oncogene Proteins - radiation effects; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - radiation effects; Radiation Tolerance; Radiation, Ionizing; Transfection; Tumor Cells, Cultured
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.1.5.174

In this study, we investigated the influence of bcl-2 overexpression on the radiosensitizing potential of Didox (DX; 3,4-Dihydroxybenzohydroxamic acid), a novel ribonucleotide reductase inhibitor, in p53-null prostate cancer cell line PC-3. The PC-3 cells were transfected with vector alone or ectopically overexpressed with CMV-bcl-2 construct. The effect of radiation (IR) or DX alone and in combination (pre and post IR exposure of DX) on cell survival was determined by colony-forming assay. The impact of these two treatments on the cell cycle was determined by flow cytometry. To further understand the molecular mechanism of DX-mediated radiosensitization, induction of pro-survival and pro-apoptotic factors were determined by Western blot and gel-shift assays respectively. When compared to PC-3/bcl-2 cells (SF2=0.84; D0=437cGy), the PC-3/vector cells (SF2=0.4; D0=235cGy) were significantly sensitive to ionizing radiation (p