title: The radiosensitizing effect of fluorocyclopentenyl-cytosine (RX-3117) in ovarian and lung cancer cell lines.
abstract: RX-3117 (fluorocyclopentenyl-cytosine) is a novel cytidine analog currently being evaluated in a Phase Ib clinical trial in cancer patients with solid tumors. The radiosensitizing effect of RX-3117 was studied in A2780 ovarian cancer cells and non-small cell lung cancer cell lines and related to cell survival and the effect on cell cycle and cell cycle proteins. RX-3117 has a schedule-dependent radiosensitizing effect, but only at pre-incubation (dose modifying factors: 1.4-1.8), observed at pulse and fractionated irradiation. Radiosensitizion was also seen in a three-dimensional spheroid model. At the low radiosensitizing concentration, RX-3117 in combination with radiation led to an accumulation of cells in S-phase, which was accompanied with an increase of cell cycle proteins such as p-Chk2 and p-cdc25C. In addition, RX-3117 caused DNA damage and increased apoptosis. In conclusion, our in vitro experiments showed a radiosensitizing effect of RX-3117.
authors.affiliation: a Department of Medical Oncology , VU University Medical Center , Amsterdam , The Netherlands.
authors.forename: Dzjemma
authors.initials: D
authors.lastname: Sarkisjan
authors.affiliation: b Department of Radio Therapy , VU University Medical Center , Amsterdam , The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: van den Berg
authors.affiliation: a Department of Medical Oncology , VU University Medical Center , Amsterdam , The Netherlands.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Smit
authors.affiliation: c Rexahn Pharmaceuticals, Inc. , Rockville , Maryland , USA.
authors.forename: Young B
authors.initials: YB
authors.lastname: Lee
authors.affiliation: c Rexahn Pharmaceuticals, Inc. , Rockville , Maryland , USA.
authors.forename: Deog J
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: a Department of Medical Oncology , VU University Medical Center , Amsterdam , The Netherlands.
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms; D010051:Ovarian Neoplasms; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
chemical_list: D011838:Radiation-Sensitizing Agents; C000589325:fluorocyclopentenylcytosine; D003562:Cytidine
keywords: DNA damage; RX-3117; cell cycle proteins; cytidine analog; radiosensitizing effect