‪Loratadine deregulates cell cycle progression and enhances‬ ‪the effect of radiation in human tumor cell lines‬

novindaroo - - اختصاصی -

‪ft is well established that the effects regulated by a complex network of nuclear translocation of Cdc25C,‬ ‪of radiation varies as a function of proteins that monitor the health of and Chk1 phosphorylation, which‬ ‪cell cycle position. Specifically, the cell. This mechanism serves to allows 14-3-3 binding to occur.‬ ‪cells in d2/M phase are particularly protect cells from potentially lethal Chk1 inhibition has been associated‬ ‪susceptible to the effects of stressors by temporarily halting cell with increased cytotoxicity of DNA‬ ‪radiation. Because of this, agents cycle progression to allow time for damaging drugs, and in our lab with‬ ‪that alter cell cycle progression are repair of damaged cell components, increased sensitivity to the effects‬ ‪often potent radiation modifiers. especially damage involving DNA. of radiation (unpublished dataF.‬ ‪Normal cell cycle regulation is For example, it is well known that Recently, loratadine has also been‬ ‪mediated by several proteins that DNA damage induced by radiation shown to cause Cdc2-associated‬ ‪are responsive to both intra- and results in cell cycle block in G2/M G2/M arrest by interfering with Chk1‬ ‪extracellular stimuli. ft has been during which time the DNA repair and Cdc25C signaling. It is likely that‬ ‪demonstrated that the commonly machinery attempts to correct the the anti-tumor effects of loratadine‬ ‪used antihistamine loratadine damage. If the damage is repaired, observed in other studies result, at‬ ‪(ethyl4-(8-chloro-5,6-dihydrocells are released from the cell least in part, from this activity.‬ ‪NNe-benzo cyclohepta pyridin-NNcycle block and are allowed to pince d2/M is a particularly‬ ‪ylidene)-1-piperidinecarboxylate), divide. Persistent DNA damage radiosensitive phase of the cell‬ ‪an antagonist of histamine may result in cell death initiated by cycle, it is logical to suggest that‬ ‪receptor-1, induces a cell cycle other surveillance mechanisms. fn the induction of a cell cycle block in‬ ‪arrest in G2/M by interfering with eukaryotic cells, the G2/M checkpoint d2/M by loratadine would enhance‬ ‪the activity of these regulatory is controlled by several proteins radiation-induced cytotoxicity,‬ ‪proteins. Although a comprehensive including cell division cycle 2 (Cdc2) however this has not yet been studied.‬ ‪mechanism was not elucidated, and Cycling B. Cdc2 is inactivated This study was initiated to determine‬ ‪in these prior studies loratadine by phosphorylation (Tyr-15, Thr-14) whether loratadine modifies the‬ ‪treatment resulted in anti-tumor and activated by Cdc25C-mediated effect of radiation on cell survival‬ ‪effects. dephosphorylating. Cdc25C, in turn, and, if so, to elucidate the mechanism‬ ‪Progression through the cell cycle is is regulated by 14-3-3, which inhibits underlying that effect.‬

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