Therapeutic potential of the cytosine deaminase::uracil phosphoribosyl transferase/5‐fluorocytosine suicide system for canine melanoma

We tested the efficacy of a yeast cytosine deaminase::uracil phosphoribosyl transferase/5‐fluorocytosine (CDU/5‐FC) non‐viral suicide system on eight established canine melanoma cell lines. Albeit with different degree of sensitivity 5 days after lipofection, this system was significantly efficient...

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Bibliographic Details
Published in:Veterinary & comparative oncology 2022-06, Vol.20 (2), p.372-380
Main Authors: Allende, Jesica B., Finocchiaro, Liliana M. E., Glikin, Gerardo C.
Format: Article
Language:English
Subjects:
5‐fluorocytosine
Animals
canine melanoma
cytosine deaminase
Cytosine Deaminase - genetics
Cytosine Deaminase - metabolism
Dog Diseases - drug therapy
Dogs
Flucytosine - metabolism
Flucytosine - pharmacology
Flucytosine - therapeutic use
ganciclovir
gene therapy
HSV‐thymidine kinase
Humans
Melanoma - drug therapy
Melanoma - veterinary
Pentosyltransferases - metabolism
Suicide
Thymidine Kinase - genetics
Uracil
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Summary:We tested the efficacy of a yeast cytosine deaminase::uracil phosphoribosyl transferase/5‐fluorocytosine (CDU/5‐FC) non‐viral suicide system on eight established canine melanoma cell lines. Albeit with different degree of sensitivity 5 days after lipofection, this system was significantly efficient killing melanoma cells, being four cell lines highly, two fairly and two not very sensitive to CDU/5‐FC (their respective IC50 ranging from 0.20 to 800 μM 5‐FC). Considering the relatively low lipofection efficiencies, a very strong bystander effect was verified in the eight cell lines: depending on the cell line, this effect accounted for most of the induced cell death (from 70% to 95%). In our assay conditions, we did not find useful interactions either with the herpes simplex thymidine kinase/ganciclovir suicide system (in sequential or simultaneous modality) or with cisplatin and bleomycin chemotherapeutic drugs. Furthermore, only two cell lines displayed limited useful interactions of the CDU/5‐FC either with interferon‐β gene transfer or the proteasome inhibitor bortezomib respectively. These results would preclude a wide use of these combinations. However, the fact that all the tested cells were significantly sensitive to the CDU/5‐FC system encourages further research as a gene therapy tool for local control of canine melanoma.
ISSN:1476-5810
1476-5829
DOI:10.1111/vco.12780