Eradication of Cancer Cells Using Doxifluridine and Mesenchymal Stem Cells Expressing Thymidine Phosphorylase
Gene-directed enzyme prodrug therapy (GDEPT) has been developed over several decades as a targeted cancer treatment aimed at minimizing toxicity to healthy cells. This approach involves three key components: a non-toxic prodrug, a gene encoding an enzyme that converts the prodrug into an active chem...
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MDPI AG
2024-11-01
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| author | Xutu Wang Ian Peng Ching-An Peng |
| author_facet | Xutu Wang Ian Peng Ching-An Peng |
| author_sort | Xutu Wang |
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| description | Gene-directed enzyme prodrug therapy (GDEPT) has been developed over several decades as a targeted cancer treatment aimed at minimizing toxicity to healthy cells. This approach involves three key components: a non-toxic prodrug, a gene encoding an enzyme that converts the prodrug into an active chemotherapy drug, and a gene carrier to target cancer cells. In this study, the prodrug doxifluridine was enzymatically converted into the chemotherapy drug 5-fluorouracil via thymidine phosphorylase, using human mesenchymal stem cells (hMSCs) as delivery vehicles. The hMSCs were first transduced with thymidine phosphorylase-encoded lentiviral vectors produced by HEK293T cells, then co-cultured with A549 adenocarcinoma cells in the presence of doxifluridine. The results showed that after 3 days of prodrug treatment, cell viability in both A549 cancer cells and hMSCs dropped by about 50%, and by day 5, viability had decreased to 10%. In summary, exogenous thymidine phosphorylase expressed in hMSCs successfully converted the non-toxic prodrug doxifluridine into the chemotherapy agent 5-fluorouracil, effectively eliminating both cancer cells and hMSCs within a short period. |
| format | Article |
| id | doaj-art-bcd56a591b974e2d9c7e6df78da5f8b2 |
| institution | OA Journals |
| issn | 2306-5354 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Bioengineering |
| spelling | doaj-art-bcd56a591b974e2d9c7e6df78da5f8b22025-08-20T02:00:51ZengMDPI AGBioengineering2306-53542024-11-011112119410.3390/bioengineering11121194Eradication of Cancer Cells Using Doxifluridine and Mesenchymal Stem Cells Expressing Thymidine PhosphorylaseXutu Wang0Ian Peng1Ching-An Peng2Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164, USADepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Chemical and Biological Engineering, University of Idaho, Moscow, ID 83844, USAGene-directed enzyme prodrug therapy (GDEPT) has been developed over several decades as a targeted cancer treatment aimed at minimizing toxicity to healthy cells. This approach involves three key components: a non-toxic prodrug, a gene encoding an enzyme that converts the prodrug into an active chemotherapy drug, and a gene carrier to target cancer cells. In this study, the prodrug doxifluridine was enzymatically converted into the chemotherapy drug 5-fluorouracil via thymidine phosphorylase, using human mesenchymal stem cells (hMSCs) as delivery vehicles. The hMSCs were first transduced with thymidine phosphorylase-encoded lentiviral vectors produced by HEK293T cells, then co-cultured with A549 adenocarcinoma cells in the presence of doxifluridine. The results showed that after 3 days of prodrug treatment, cell viability in both A549 cancer cells and hMSCs dropped by about 50%, and by day 5, viability had decreased to 10%. In summary, exogenous thymidine phosphorylase expressed in hMSCs successfully converted the non-toxic prodrug doxifluridine into the chemotherapy agent 5-fluorouracil, effectively eliminating both cancer cells and hMSCs within a short period.https://www.mdpi.com/2306-5354/11/12/1194gene-directed enzyme prodrug therapymesenchymal stem celllentiviral vectorthymidine phosphorylasedoxifluridine5-fluorouracil |
| spellingShingle | Xutu Wang Ian Peng Ching-An Peng Eradication of Cancer Cells Using Doxifluridine and Mesenchymal Stem Cells Expressing Thymidine Phosphorylase Bioengineering gene-directed enzyme prodrug therapy mesenchymal stem cell lentiviral vector thymidine phosphorylase doxifluridine 5-fluorouracil |
| title | Eradication of Cancer Cells Using Doxifluridine and Mesenchymal Stem Cells Expressing Thymidine Phosphorylase |
| title_full | Eradication of Cancer Cells Using Doxifluridine and Mesenchymal Stem Cells Expressing Thymidine Phosphorylase |
| title_fullStr | Eradication of Cancer Cells Using Doxifluridine and Mesenchymal Stem Cells Expressing Thymidine Phosphorylase |
| title_full_unstemmed | Eradication of Cancer Cells Using Doxifluridine and Mesenchymal Stem Cells Expressing Thymidine Phosphorylase |
| title_short | Eradication of Cancer Cells Using Doxifluridine and Mesenchymal Stem Cells Expressing Thymidine Phosphorylase |
| title_sort | eradication of cancer cells using doxifluridine and mesenchymal stem cells expressing thymidine phosphorylase |
| topic | gene-directed enzyme prodrug therapy mesenchymal stem cell lentiviral vector thymidine phosphorylase doxifluridine 5-fluorouracil |
| url | https://www.mdpi.com/2306-5354/11/12/1194 |
| work_keys_str_mv | AT xutuwang eradicationofcancercellsusingdoxifluridineandmesenchymalstemcellsexpressingthymidinephosphorylase AT ianpeng eradicationofcancercellsusingdoxifluridineandmesenchymalstemcellsexpressingthymidinephosphorylase AT chinganpeng eradicationofcancercellsusingdoxifluridineandmesenchymalstemcellsexpressingthymidinephosphorylase |