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

Radiation Oncology
Benjamin P SouleJames B Mitchell

Abstract

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). 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, pChk1(ser345), and Cyclin B was analyzed by western blot. Loratadine pre-treatment of exponentially growing cells (75 microM, 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 pChk1(ser345), however a subs...Continue Reading

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Citations

Jul 12, 2012·Clinical Oral Investigations·Martin GrimmSebastian Hoefert
Mar 20, 2014·Drug and Chemical Toxicology·Seval Kontaş, Zülal Atlı Şekeroğlu
Apr 2, 2016·Oxidative Medicine and Cellular Longevity·Deborah BauerAnderson Junger Teodoro
Jul 20, 2010·British Journal of Pharmacology·Vanina A Medina, Elena S Rivera
Mar 22, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Su BoSu Qi
Dec 18, 2016·Life Sciences·Ana I Faustino-RochaMário Ginja
Mar 8, 2017·Chemical Biology & Drug Design·Yasodakrishna SajjaJagadeesh Babu Nanubolu
Nov 11, 2018·British Journal of Pharmacology·Noelia A MassariVanina A Medina
Mar 1, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrew J LeikerJames B Mitchell
Jun 25, 2020·Journal of the American Chemical Society·Elizabeth A StoneScott J Miller

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Methods Mentioned

BETA
nuclear translocation
protein assay
Electrophoresis
flow cytometry
Protein Asssay

Software Mentioned

AlphaEaseFC
- Fit
MOD
CellQuest

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