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Title 

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

Authors 

M S MoonJ S KimT L KimJ J YumEun Wie ChoI G Kim

Publisher 

Springer Verlag (Germany)

Issue Date 

2006

Citation 

Cell Biology and Toxicology, vol. 22, no. 2, pp. 137-147

Keywords 

cell cycle delaycyclin D1DFMOHSP25polyamineradiation-induced cell deaththioredoxincell culture

Abstract 

In previous studies, polyamine depletion by DFMO (α- difluoromethylornithine)-treatment reduced H2O2-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 G2/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 G2/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 γ-irradiation- induced G2/M phase arrest was also significantly delayed and radiation-induced cell death was profoundly reduced, as in the DFMO-treated cells. Both sets of cells showed a decrease of cyclin D1 and an increment of HSP25, which are involved in radiation-induced cell cycle progress. Overall, these results suggest that polyamines are essential for normal cell death of HT29 cells triggered by γ-radiation and that this is partially mediated by the regulation of thioredoxin expression.

ISSN 

0742-2091

Link 

http://dx.doi.org/10.1007/s10565-006-0042-z

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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