| Title | Photodynamic therapy-driven induction of suicide cytosine deaminase gene. | | Author(s) | Bil J, Wlodarski P, Winiarska M, Kurzaj Z, Issat T, Jozkowicz A, Wegiel B, Dulak J, Golab J | | Institution | Department of Immunology, Center of Biostructure Research, Medical University of Warsaw, 02-097 Warsaw, Poland. | | Source | Cancer Lett 2009 Oct 10. | | Abstract | Photodynamic therapy (PDT) of tumors is associated with induction of hypoxia that results in activation of hypoxia-inducible factors (HIFs). Several observations indicate that increased HIFs transcriptional activity in tumor cells is associated with cytoprotective responses that limit cytotoxic effectiveness of PDT. Therefore, we decided to examine whether this cytoprotective mechanism could be intentionally used for designing more efficient tumor cell cytotoxicity. To this end we transfected tumor cells with a plasmid vector carrying a suicide cytosine deaminase gene driven by a promoter containing hypoxia response elements (HRE). The presence of such a genetic molecular beacon rendered tumor cells sensitive to cytotoxic effects of a non-toxic prodrug 5-fluorocytosine (5-FC). The results of this study provides a proof of concept that inducible cytoprotective mechanisms can be exploited to render tumor cells more susceptible to cytotoxic effects of prodrugs activated by products of suicide genes. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19822393 |
|
