Back to Search
Start Over
Effects of genetically engineered stem cells expressing cytosine deaminase and interferon-beta or carboxyl esterase on the growth of LNCaP rrostate cancer cells.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2012 Sep 28; Vol. 13 (10), pp. 12519-32. Date of Electronic Publication: 2012 Sep 28. - Publication Year :
- 2012
-
Abstract
- The risk of prostate cancer has been increasing in men by degrees. To develop a new prostate cancer therapy, we used a stem cell-derived gene directed prodrug enzyme system using human neural stem cells (hNSCs) that have a tumor-tropic effect. These hNSCs were transduced with the therapeutic genes for bacterial cytosine deaminase (CD), alone or in combination with the one encoding human interferon-beta (IFN-β) or rabbit carboxyl esterase (CE) to generate HB1.F3.CD, HB1.F3.CD.IFN-β, and HB1.F3.CE cells, respectively. CD enzyme can convert the prodrug 5-fluorocytosine (5-FC) into the activated form 5-fluorouracil (5-FU). In addition, CE enzyme can convert the prodrug CPT-11 into a toxic agent, SN-38. In our study, the human stem cells were found to migrate toward LNCaP human prostate cancer cells rather than primary cells. This phenomenon may be due to interactions between chemoattractant ligands and receptors, such as VEGF/VEGFR2 and SCF/c-Kit, expressed as cancer and stem cells, respectively. The HB1.F3.CE, HB.F3.CD, or HB1.F3.CD.IFN-β cells significantly reduced the LNCaP cell viability in the presence of the prodrugs 5-FC or CPT-11. These results indicate that stem cells expressing therapeutic genes can be used to develop a new strategy for selectively treating human prostate cancer.
- Subjects :
- Animals
Camptothecin analogs & derivatives
Camptothecin chemistry
Camptothecin metabolism
Camptothecin toxicity
Carboxylesterase genetics
Cell Line, Tumor
Cell Movement drug effects
Cell Proliferation drug effects
Cell Survival drug effects
Coculture Techniques
Cytosine Deaminase genetics
Flucytosine chemistry
Flucytosine metabolism
Fluorouracil chemistry
Fluorouracil metabolism
Fluorouracil toxicity
Genetic Engineering
Humans
Interferon-beta genetics
Irinotecan
Male
Prodrugs chemistry
Prodrugs metabolism
Prostatic Neoplasms metabolism
Prostatic Neoplasms pathology
Rabbits
Stem Cells cytology
Carboxylesterase metabolism
Cytosine Deaminase metabolism
Interferon-beta metabolism
Stem Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 13
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 23202910
- Full Text :
- https://doi.org/10.3390/ijms131012519