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

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 ectopi...

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Bibliographic Details
Published in:Cancer biology & therapy 2002-09, Vol.1 (5), p.539-545
Main Authors: Inayat, Mohammed S., Chendil, Damodaran, Mohiuddin, Mohammed, Elford, Howard L., Gallicchio, Vincent S., Ahmed, Mansoor M.
Format: Article
Language:English
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
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Summary: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
ISSN:1538-4047
1555-8576
DOI:10.4161/cbt.1.5.174