RNA Cleavage and Inhibition of Protein Synthesis by Bleomycin
| Autor: | Jih Jing Lin, Sidney M. Hecht, Anil T. Abraham, Dianne L. Newton, Susanna M. Rybak |
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| Rok vydání: | 2003 |
| Předmět: |
Reticulocytes
Xenopus Clinical Biochemistry Drug Evaluation Preclinical Antineoplastic Agents Biology 010402 general chemistry Cleavage (embryo) Bleomycin 01 natural sciences Biochemistry 03 medical and health sciences chemistry.chemical_compound Ribonucleases Cell Line Tumor Drug Discovery medicine Protein biosynthesis Animals Humans Ribonuclease Molecular Biology 030304 developmental biology Protein Synthesis Inhibitors Pharmacology 0303 health sciences Cell-Free System RNA General Medicine respiratory system Molecular biology 3. Good health 0104 chemical sciences Mechanism of action chemistry Protein Biosynthesis Transfer RNA Oocytes biology.protein Molecular Medicine Rabbits RNA Cleavage medicine.symptom Software |
| Zdroj: | Chemistry & Biology. 10:45-52 |
| ISSN: | 1074-5521 |
| Popis: | Bleomycin is a clinically used antitumor antibiotic long thought to function therapeutically at the level of DNA cleavage. Recently, it has become clear that bleomycin can also cleave selected members of all major classes of RNA. Using the computer program COMPARE to search the database established by the Anticancer Drug Screening Program of the National Cancer Institute, a possible mechanism-based correlation was found between onconase, an antitumor ribonuclease currently being evaluated in phase III clinical trials, and the chemotherapeutic agent bleomycin. Following these observations, experimentation revealed that bleomycin caused tRNA cleavage and DNA-independent protein synthesis inhibition in rabbit reticulocyte lysate and when microinjected into Xenopus oocytes. The correlation of protein synthesis inhibition to the previously reported site-specific RNA cleavage caused by bleomycin supports the thesis that RNA cleavage may constitute an important element of the mechanism of action of bleomycin. |
| Databáze: | OpenAIRE |
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