PURPOSE: To determine the effects of combinations of radiation and flavopiridol, an inhibitor of cyclin-dependent kinases and global transcription, in a human uterine cervix cancer cell line. MATERIALS AND METHODS: Human uterine cervix cancer cells (HeLa), cultured to the mid-log phase, were exposed to X-rays, flavopiridol, and combinations of X-rays and flavopiridol in various sequences. The end point in this study was the clonogenic survival, which was measured via clonogenic assays. In order to determine the intrinsic cytotoxicity of flavopiridol, 0, 5, 12.5, 25, 37.5, 50 and 100 nM of flavopiridol were added to cell culture media. In the combination treatment, four different schedules of flavopiridol and irradiation combinations were tested: treatment of flavopiridol for 24 hours followed by irradiation, simultaneous administration of flavopiridol and irradiation, and irradiation followed by flavopiridol (for 24 hours) at intervals of 6 and 24 hours. The fraction of cells surviving after the combination treatment with 2 Gy of radiation (SF2) was compared with that of the fraction of cells surviving after treatment with irradiation alone. RESULTS: The cytotoxicity of flavopiridol was found to be dose-dependent, with an IC50 of 80 nM. No cytotoxic enhancements were observed when flavopiridol and radiation were administered simultaneously. Flavopiridol, administered either 24 hours before or 6 hours after irradiation, exerted no sensitizing effects on the cells. Only one protocol resulted in a radiosensitizing effect: the administration of flavopiridol 24 hours after irradiation. CONCLUSION: Flavopiridol enhanced the effects of radiation on a uterine cervix cancer cell line in vitro, and this enhancement was both sequence- and time-dependent.
PURPOSE: To determine the effects of combinations of radiation and flavopiridol, an inhibitor of cyclin-dependent kinases and global transcription, in a human uterine cervix cancer cell line. MATERIALS AND METHODS:Human uterine cervix cancer cells (HeLa), cultured to the mid-log phase, were exposed to X-rays, flavopiridol, and combinations of X-rays and flavopiridol in various sequences. The end point in this study was the clonogenic survival, which was measured via clonogenic assays. In order to determine the intrinsic cytotoxicity of flavopiridol, 0, 5, 12.5, 25, 37.5, 50 and 100 nM of flavopiridol were added to cell culture media. In the combination treatment, four different schedules of flavopiridol and irradiation combinations were tested: treatment of flavopiridol for 24 hours followed by irradiation, simultaneous administration of flavopiridol and irradiation, and irradiation followed by flavopiridol (for 24 hours) at intervals of 6 and 24 hours. The fraction of cells surviving after the combination treatment with 2 Gy of radiation (SF2) was compared with that of the fraction of cells surviving after treatment with irradiation alone. RESULTS: The cytotoxicity of flavopiridol was found to be dose-dependent, with an IC50 of 80 nM. No cytotoxic enhancements were observed when flavopiridol and radiation were administered simultaneously. Flavopiridol, administered either 24 hours before or 6 hours after irradiation, exerted no sensitizing effects on the cells. Only one protocol resulted in a radiosensitizing effect: the administration of flavopiridol 24 hours after irradiation. CONCLUSION:Flavopiridol enhanced the effects of radiation on a uterine cervix cancer cell line in vitro, and this enhancement was both sequence- and time-dependent.
Entities:
Keywords:
Flavopiridol; Radiation; Uterine cervix cancer
Authors: H Sedlacek; J Czech; R Naik; G Kaur; P Worland; M Losiewicz; B Parker; B Carlson; A Smith; A Senderowicz; E Sausville Journal: Int J Oncol Date: 1996-12 Impact factor: 5.650
Authors: Elizabeth W Newcomb; Cristina Tamasdan; Yolanda Entzminger; Judith Alonso; David Friedlander; Diana Crisan; Douglas C Miller; David Zagzag Journal: Cell Cycle Date: 2003 May-Jun Impact factor: 4.534
Authors: V Patel; A M Senderowicz; D Pinto; T Igishi; M Raffeld; L Quintanilla-Martinez; J F Ensley; E A Sausville; J S Gutkind Journal: J Clin Invest Date: 1998-11-01 Impact factor: 14.808
Authors: Young Eun Lee; Seung Ah Choi; Pil Ae Kwack; Hak Jae Kim; Il Han Kim; Kyu-Chang Wang; Ji Hoon Phi; Ji Yeoun Lee; Sangjoon Chong; Sung-Hye Park; Kyung Duk Park; Do Won Hwang; Kyeung Min Joo; Seung-Ki Kim Journal: Neuro Oncol Date: 2017-08-01 Impact factor: 12.300
Authors: Marco Calvaruso; Gaia Pucci; Rosa Musso; Valentina Bravatà; Francesco P Cammarata; Giorgio Russo; Giusi I Forte; Luigi Minafra Journal: Int J Mol Sci Date: 2019-10-23 Impact factor: 5.923