Characterization of a transport and detoxification pathway for the antitumour drug bleomycin in Saccharomyces cerevisiae

The Biochemical Journal
Mustapha AouidaDindial Ramotar

Abstract

BLM (bleomycin) is effective in combination therapy against various cancers including testicular cancer. However, several other cancers such as colon cancer are refractory to BLM treatment. The exact mechanism for this differential response of cancer cells to the drug is not known. In the present study, we created fluorescently labelled BLM-A5, which retained nearly full genotoxic potential, and used this molecule to conduct the first study to understand the transport pathway of the drug in Saccharomyces cerevisiae. Uptake studies revealed that fluoro-BLM-A5 is transported into the cell in a concentration-dependent manner. Transport of a non-saturating concentration of fluoro-BLM-A5 was modest for the first 90 min, but thereafter it was sharply induced until 300 min. The inducible transport was completely abolished by the addition of cycloheximide, suggesting that BLM-A5 uptake into the cell is dependent on new protein synthesis. Interestingly, transport of fluoro-BLM-A5 was blocked if the cells were preincubated with increasing concentrations of spermine. Moreover, a mutant lacking the Ptk2 kinase, necessary for positively regulating polyamine transport, was defective in fluoro-BLM-A5 uptake and exhibited extreme resistance to...Continue Reading

References

Oct 1, 1977·Nucleic Acids Research·L F PovirkF Hutchinson
Mar 25, 1992·Nucleic Acids Research·D GietzR H Schiestl
Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·R J Steighner, L F Povirk
Mar 1, 1991·Mutation Research·L F Povirk, M J Austin
Jan 1, 1991·Methods in Enzymology·V DulicH Riezman
Jan 1, 1971·Pure and Applied Chemistry. Chimie Pure Et Appliquée·H Umezawa
Jul 15, 1993·Biochemical and Biophysical Research Communications·G PronL M Mir
Jun 1, 1996·Journal of Neurosurgery·G Broggi, A Franzini
Oct 23, 1997·International Journal of Cancer. Journal International Du Cancer·W BergerM Micksche
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·M GhoshB P Rosen
Jan 29, 2000·Journal of Natural Products·S M Hecht
Feb 19, 2002·Chemical Reviews·Richard M. Burger
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Lawrence H Einhorn

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Citations

Feb 3, 2005·Nature Reviews. Cancer·Jingyang Chen, JoAnne Stubbe
Dec 29, 2009·The Journal of Biological Chemistry·Mustapha AouidaDindial Ramotar
Nov 27, 2009·The Journal of Biological Chemistry·Tania MassignanDavid A Harris
Oct 29, 2011·The Journal of Biological Chemistry·Rohitashw KumarMira Edgerton
Sep 22, 2009·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Mustapha AouidaDindial Ramotar
Apr 20, 2007·Biochemical and Biophysical Research Communications·Angela T Y TamJörg Heierhorst
Nov 2, 2006·Environmental and Molecular Mutagenesis·Kaouther TounektiDindial Ramotar
Jul 12, 2005·Yeast
Apr 28, 2005·The Journal of Biological Chemistry·Mustapha AouidaDindial Ramotar

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