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Mycoplasma hyorhinis-encoded cytidine deaminase efficiently inactivates cytosine-based anticancer drugs.

Vande Voorde J, Vervaeke P, Liekens S, Balzarini J - FEBS Open Bio (2015)

Bottom Line: This mycoplasma-driven drug deamination could be prevented by exogenous administration of the cytidine deaminase (CDA) inhibitor tetrahydrouridine, but also by the natural nucleosides or by a purine nucleoside phosphorylase inhibitor.The M. hyorhinis-encoded CDAHyor gene was cloned, expressed as a recombinant protein and purified.CDAHyor was found to be more catalytically active than its human equivalent and efficiently deaminates (inactivates) cytosine-based anticancer drugs.

View Article: PubMed Central - PubMed

Affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, blok x - bus 1030, B-3000 Leuven, Belgium.

ABSTRACT
Mycoplasmas may colonize tumor tissue in patients. The cytostatic activity of gemcitabine was dramatically decreased in Mycoplasma hyorhinis-infected tumor cell cultures compared with non-infected tumor cell cultures. This mycoplasma-driven drug deamination could be prevented by exogenous administration of the cytidine deaminase (CDA) inhibitor tetrahydrouridine, but also by the natural nucleosides or by a purine nucleoside phosphorylase inhibitor. The M. hyorhinis-encoded CDAHyor gene was cloned, expressed as a recombinant protein and purified. CDAHyor was found to be more catalytically active than its human equivalent and efficiently deaminates (inactivates) cytosine-based anticancer drugs. CDAHyor expression at the tumor site may result in selective drug inactivation and suboptimal therapeutic efficiency.

No MeSH data available.


Related in: MedlinePlus

Kinetic analysis of CDAHyor- and CDAHuman-catalyzed deamination of natural nucleosides and nucleoside analogues Deamination of different concentrations of Cyd (A and B), dCyd (C and D), dFdC (E and F) and ara-Cyd (G and H) by CDAHyor (A, C, E and G) or CDAHuman (B, D, F and H). The data are the mean of at least two independent experiments (±S.E.M.).
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f0020: Kinetic analysis of CDAHyor- and CDAHuman-catalyzed deamination of natural nucleosides and nucleoside analogues Deamination of different concentrations of Cyd (A and B), dCyd (C and D), dFdC (E and F) and ara-Cyd (G and H) by CDAHyor (A, C, E and G) or CDAHuman (B, D, F and H). The data are the mean of at least two independent experiments (±S.E.M.).

Mentions: The kinetic parameters (KM and kcat) for CDAHyor- and CDAHuman-catalyzed deamination of Cyd, dCyd, dFdC and ara-Cyd were determined. Relatively high KM values (ranging from high micromolar to low millimolar concentrations) were observed for both enzymes. CDAHyor typically displayed higher KM values compared with CDAHuman (Tables 2 and 3 and Fig. 4). However, the catalytic efficiency (calculated as kcat/KM) of CDAHyor-catalyzed reactions was ∼2–4 fold higher compared with CDAHuman (Tables 2 and 3).


Mycoplasma hyorhinis-encoded cytidine deaminase efficiently inactivates cytosine-based anticancer drugs.

Vande Voorde J, Vervaeke P, Liekens S, Balzarini J - FEBS Open Bio (2015)

Kinetic analysis of CDAHyor- and CDAHuman-catalyzed deamination of natural nucleosides and nucleoside analogues Deamination of different concentrations of Cyd (A and B), dCyd (C and D), dFdC (E and F) and ara-Cyd (G and H) by CDAHyor (A, C, E and G) or CDAHuman (B, D, F and H). The data are the mean of at least two independent experiments (±S.E.M.).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4541722&req=5

f0020: Kinetic analysis of CDAHyor- and CDAHuman-catalyzed deamination of natural nucleosides and nucleoside analogues Deamination of different concentrations of Cyd (A and B), dCyd (C and D), dFdC (E and F) and ara-Cyd (G and H) by CDAHyor (A, C, E and G) or CDAHuman (B, D, F and H). The data are the mean of at least two independent experiments (±S.E.M.).
Mentions: The kinetic parameters (KM and kcat) for CDAHyor- and CDAHuman-catalyzed deamination of Cyd, dCyd, dFdC and ara-Cyd were determined. Relatively high KM values (ranging from high micromolar to low millimolar concentrations) were observed for both enzymes. CDAHyor typically displayed higher KM values compared with CDAHuman (Tables 2 and 3 and Fig. 4). However, the catalytic efficiency (calculated as kcat/KM) of CDAHyor-catalyzed reactions was ∼2–4 fold higher compared with CDAHuman (Tables 2 and 3).

Bottom Line: This mycoplasma-driven drug deamination could be prevented by exogenous administration of the cytidine deaminase (CDA) inhibitor tetrahydrouridine, but also by the natural nucleosides or by a purine nucleoside phosphorylase inhibitor.The M. hyorhinis-encoded CDAHyor gene was cloned, expressed as a recombinant protein and purified.CDAHyor was found to be more catalytically active than its human equivalent and efficiently deaminates (inactivates) cytosine-based anticancer drugs.

View Article: PubMed Central - PubMed

Affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, blok x - bus 1030, B-3000 Leuven, Belgium.

ABSTRACT
Mycoplasmas may colonize tumor tissue in patients. The cytostatic activity of gemcitabine was dramatically decreased in Mycoplasma hyorhinis-infected tumor cell cultures compared with non-infected tumor cell cultures. This mycoplasma-driven drug deamination could be prevented by exogenous administration of the cytidine deaminase (CDA) inhibitor tetrahydrouridine, but also by the natural nucleosides or by a purine nucleoside phosphorylase inhibitor. The M. hyorhinis-encoded CDAHyor gene was cloned, expressed as a recombinant protein and purified. CDAHyor was found to be more catalytically active than its human equivalent and efficiently deaminates (inactivates) cytosine-based anticancer drugs. CDAHyor expression at the tumor site may result in selective drug inactivation and suboptimal therapeutic efficiency.

No MeSH data available.


Related in: MedlinePlus