RNA cleavage and inhibition of protein synthesis by Bleomycin

Anil T. Abraham, Jih Jing Lin, Dianne L. Newton, Susanna Rybak, Sidney Hecht

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalChemistry and Biology
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

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RNA Cleavage
Bleomycin
RNA
DNA Cleavage
Proteins
Phase III Clinical Trials
Preclinical Drug Evaluations
National Cancer Institute (U.S.)
Reticulocytes
DNA
Ribonucleases
Xenopus
Transfer RNA
Oocytes
Computer program listings
Screening
Software
Databases
Anti-Bacterial Agents
Rabbits

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

RNA cleavage and inhibition of protein synthesis by Bleomycin. / Abraham, Anil T.; Lin, Jih Jing; Newton, Dianne L.; Rybak, Susanna; Hecht, Sidney.

In: Chemistry and Biology, Vol. 10, No. 1, 01.01.2003, p. 45-52.

Research output: Contribution to journalArticle

Abraham, Anil T. ; Lin, Jih Jing ; Newton, Dianne L. ; Rybak, Susanna ; Hecht, Sidney. / RNA cleavage and inhibition of protein synthesis by Bleomycin. In: Chemistry and Biology. 2003 ; Vol. 10, No. 1. pp. 45-52.
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