Polyamine depletion partially reduces the radiation-induced cell death via cell cycle delay mediated by thioredoxin

Cell Biology and Toxicology
M S MoonI G Kim

Abstract

In previous studies, polyamine depletion by DFMO (alpha-difluoromethylornithine)-treatment reduced H(2)O(2)-induced apoptotic cell death by reduction of ferric ion uptake. In the present study, we analyzed the reduction of radiation-induced cell death by polyamine depletion. Exposure of HT29 cells to radiation induced severe cell death, but when cells were pretreated with DFMO, a specific inhibitor of polyamine biosynthesis, radiation-induced cell death was reduced to 50-60% of control. Cell cycle analysis showed that, in these cells, the time to reach the G(2)/M phase arrest was delayed for 20-24 h compared to the control cells, at which stage the fate of cells exposed to ionizing radiation is determined. DFMO-treated cells also showed a low level of thioredoxin, which is a high-level determinant of the cellular fate. To investigate the relationship between the G(2)/M phase arrest and the reduction of thioredoxin caused by polyamine depletion, we also analyzed thioredoxin-antisensed (asTRX) HT29 cells as for DFMO-treated cells. In asTRX-transfected cells, the gamma-irradiation-induced G(2)/M phase arrest was also significantly delayed and radiation-induced cell death was profoundly reduced, as in the DFMO-treated cells. Both s...Continue Reading

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Citations

Apr 6, 2011·Cancer Prevention Research·Gerardo G MackenzieBasil Rigas
Oct 10, 2008·The British Journal of Radiology·A Mukherjee, S G Martin
Nov 17, 2017·Stem Cell Research & Therapy·Pasupathi SundaramoorthyYubin Kang

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