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Impact of JNK1, JNK2, and ligase Itch on reactive oxygen species formation and survival of prostate cancer cells treated with diallyl trisulfide.
MedLine Citation:
PMID:  21863240     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: In our previous study, we demonstrated that diallyl trisulfide (DATS) induced iron-dependent G2-M arrest of prostate cancer cell cycle. Moreover, ferritin degradation and an increase of labile iron pool has been linked to the activation of the JNK signaling axis. In the present work, we extended this study to determine which of the c-jun kinases is responsible for ferritin degradation and the role of iron in DATS-induced cell death. We hypothesized that JNK1 activates Itch ligase which will lead to ferritin ubiquitination, an increase in iron-dependent ROS formation and cell death. METHODS: PC-3 prostate cancer cells were used in this study. Cell viability, concentration of ROS, labile iron pool, and changes in ferritin and P-Itch and DNA damage were determined. RESULTS: We observed that DATS induced ferritin degradation through JNK, Itch signaling axis. DATS did not induce neither ROS formation nor increase the LIP in JNK1-DN transfected cells. We also observed that DATS increased JNK-dependent activating phosphorylation of E3ligase Itch. The cells transfected with inactive form of Itch were more resistant against cytotoxicity of DATS and showed lower DATS-induced ferritin degradation. Desferrioxamine a specific iron chelator had no effect neither on cell viability nor DNA damage evaluated by comet assay. CONCLUSIONS: These results suggest that JNK1-dependent increase in LIP is mediated by Itch ubiquitin ligase.
Authors:
Alicja Sielicka-Dudzin; Andzelika Borkowska; Anna Herman-Antosiewicz; Michal Wozniak; Agnieszka Jozwik; Donatella Fedeli; Jedrzej Antosiewicz
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-24
Journal Detail:
Title:  European journal of nutrition     Volume:  -     ISSN:  1436-6215     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888704     Medline TA:  Eur J Nutr     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Bioenergetics and Physiology of Exercise, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, Poland.
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