Mycoplasma hyorhinis-encoded cytidine deaminase efficiently inactivates cytosine-based anticancer drugs
| Autor: | Peter Vervaeke, Sandra Liekens, Jan Balzarini, Johan Vande Voorde |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
QH301-705.5
Mycoplasma hyorhinis Deamination Purine nucleoside phosphorylase NA nucleoside analogue Biology ddC 2′ 3′-dideoxycytidine General Biochemistry Genetics and Molecular Biology law.invention chemistry.chemical_compound (d)Ado (2′-deoxy)adenosine Mycoplasma dFdU 2′ 2′-difluoro-2′-deoxyuridine law PNP purine nucleoside phosphorylase Research article (d)Ino (2′-deoxy)inosine dThd thymidine Tetrahydrouridine Biology (General) Cancer dFdC gemcitabine (d)Guo (2′-deoxy)guanosine Cytidine deaminase Imm-H Immucillin-H Nucleoside analogue biology.organism_classification Gemcitabine 3TC 2′ 3′-dideoxy-3′-thiacytidine (d)Urd (2′-deoxy)uridine Biochemistry chemistry Recombinant DNA ara-Cyd cytosine arabinoside Thymidine Cytosine CDA cytidine deaminase |
| Zdroj: | FEBS Open Bio, Vol 5, Iss 1, Pp 634-639 (2015) FEBS Open Bio |
| ISSN: | 2211-5463 |
| DOI: | 10.1016/j.fob.2015.07.007 |
| Popis: | Highlights • Mycoplasmas may colonize tumor tissue in patients. • Mycoplasma-encoded cytidine deaminase deaminates cytosine-based anticancer drugs. • The activity of gemcitabine is compromised in mycoplasma-infected tumor cells. • Gemcitabine activity can be restored by nucleosides or a PNP inhibitor. 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. |
| Databáze: | OpenAIRE |
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