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Báo cáo khoa học: " Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Radiation Oncology cung cấp cho các bạn kiến thức về ngành y đề tài: Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines. | Soule et al. Radiation Oncology 2010 5 8 http www.ro-journal.eom content 5 1 8 RADIATION ONCOLOGY RESEARCH Open Access Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines Benjamin P Soule Nicole L Simone William G DeGraff Rajani Choudhuri John A Cook James B Mitchell Abstract Background The histamine receptor-1 H1 -antagonist loratadine has been shown to inhibit growth of human colon cancer xenografts in part due to cell cycle arrest in G2 M. Since this is a radiation sensitive phase of the cell cycle we sought to determine if loratadine modifies radiosensitivity in several human tumor cell lines with emphasis on human colon carcinoma HT29 . Methods Cells were treated with several doses of loratadine at several time points before and after exposure to radiation. Radiation dose modifying factors DMF were determined using full radiation dose response survival curves. Cell cycle phase was determined by flow cytometry and the expression of the cell cycle-associated proteins Chk1 pChk1ser345 and Cyclin B was analyzed by western blot. Results Loratadine pre-treatment of exponentially growing cells 75 uM 24 hours increased radiation-induced cytotoxicity yielding a radiation DMF of 1.95. However treatment of plateau phase cells also yielded a DMF of 1.3 suggesting that mechanisms other than cell cycle arrest also contribute to loratadine-mediated radiation modification. Like irradiation loratadine initially induced G2 M arrest and activation of the cell-cycle associated protein Chk1 to pChk1ser345 however a subsequent decrease in expression of total Chk1 and Cyclin B correlated with abrogation of the G2 M checkpoint. Analysis of DNA repair enzyme expression and DNA fragmentation revealed a distinct pattern of DNA damage in loratadine-treated cells in addition to enhanced radiation-induced damage. Taken together these data suggest that the observed effects of loratadine are multifactorial in that loratadine 1 .