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c-Jun NH(2)-terminal kinase signaling axis regulates diallyl trisulfide-induced generation of reactive oxygen species and cell cycle arrest in human prostate cancer cells.
Cancer Res 2006; 66(10):5379-86CR

Abstract

We have shown previously that generation of reactive oxygen species (ROS) is a critical event in G(2)-M phase cell cycle arrest caused by diallyl trisulfide (DATS), which is a highly promising anticancer constituent of processed garlic. Using DU145 and PC-3 human prostate cancer cells as a model, we now report a novel mechanism involving c-Jun NH(2)-terminal kinase (JNK) signaling axis, which is known for its role in regulation of cell survival and apoptosis, in DATS-induced ROS production. The DATS-induced ROS generation, G(2)-M phase cell cycle arrest and degradation, and hyperphosphorylation of Cdc25C were significantly attenuated in the presence of EUK134, a combined mimetic of superoxide dismutase and catalase. Interestingly, the DATS-induced ROS generation and G(2)-M phase cell cycle arrest were also inhibited significantly in the presence of desferrioxamine, an iron chelator, but this protection was not observed with iron-saturated desferrioxamine. DATS treatment caused a marked increase in the level of labile iron that was accompanied by degradation of light chain of iron storage protein ferritin. Interestingly, DATS-mediated degradation of ferritin, increase in labile iron pool, ROS generation, and/or cell cycle arrest were significantly attenuated by ectopic expression of a catalytically inactive mutant of JNK kinase 2 and RNA interference of stress-activated protein kinase/extracellular signal-regulated kinase 1 (SEK1), upstream kinases in JNK signal transduction pathway. In conclusion, the present study provides experimental evidence to indicate existence of a novel pathway involving JNK signaling axis in regulation of DATS-induced ROS generation.

Authors+Show Affiliations

Department of Pharmacology and Urology and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16707465

Citation

Antosiewicz, Jedrzej, et al. "C-Jun NH(2)-terminal Kinase Signaling Axis Regulates Diallyl Trisulfide-induced Generation of Reactive Oxygen Species and Cell Cycle Arrest in Human Prostate Cancer Cells." Cancer Research, vol. 66, no. 10, 2006, pp. 5379-86.
Antosiewicz J, Herman-Antosiewicz A, Marynowski SW, et al. C-Jun NH(2)-terminal kinase signaling axis regulates diallyl trisulfide-induced generation of reactive oxygen species and cell cycle arrest in human prostate cancer cells. Cancer Res. 2006;66(10):5379-86.
Antosiewicz, J., Herman-Antosiewicz, A., Marynowski, S. W., & Singh, S. V. (2006). C-Jun NH(2)-terminal kinase signaling axis regulates diallyl trisulfide-induced generation of reactive oxygen species and cell cycle arrest in human prostate cancer cells. Cancer Research, 66(10), pp. 5379-86.
Antosiewicz J, et al. C-Jun NH(2)-terminal Kinase Signaling Axis Regulates Diallyl Trisulfide-induced Generation of Reactive Oxygen Species and Cell Cycle Arrest in Human Prostate Cancer Cells. Cancer Res. 2006 May 15;66(10):5379-86. PubMed PMID: 16707465.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - c-Jun NH(2)-terminal kinase signaling axis regulates diallyl trisulfide-induced generation of reactive oxygen species and cell cycle arrest in human prostate cancer cells. AU - Antosiewicz,Jedrzej, AU - Herman-Antosiewicz,Anna, AU - Marynowski,Stanley W, AU - Singh,Shivendra V, PY - 2006/5/19/pubmed PY - 2006/7/19/medline PY - 2006/5/19/entrez SP - 5379 EP - 86 JF - Cancer research JO - Cancer Res. VL - 66 IS - 10 N2 - We have shown previously that generation of reactive oxygen species (ROS) is a critical event in G(2)-M phase cell cycle arrest caused by diallyl trisulfide (DATS), which is a highly promising anticancer constituent of processed garlic. Using DU145 and PC-3 human prostate cancer cells as a model, we now report a novel mechanism involving c-Jun NH(2)-terminal kinase (JNK) signaling axis, which is known for its role in regulation of cell survival and apoptosis, in DATS-induced ROS production. The DATS-induced ROS generation, G(2)-M phase cell cycle arrest and degradation, and hyperphosphorylation of Cdc25C were significantly attenuated in the presence of EUK134, a combined mimetic of superoxide dismutase and catalase. Interestingly, the DATS-induced ROS generation and G(2)-M phase cell cycle arrest were also inhibited significantly in the presence of desferrioxamine, an iron chelator, but this protection was not observed with iron-saturated desferrioxamine. DATS treatment caused a marked increase in the level of labile iron that was accompanied by degradation of light chain of iron storage protein ferritin. Interestingly, DATS-mediated degradation of ferritin, increase in labile iron pool, ROS generation, and/or cell cycle arrest were significantly attenuated by ectopic expression of a catalytically inactive mutant of JNK kinase 2 and RNA interference of stress-activated protein kinase/extracellular signal-regulated kinase 1 (SEK1), upstream kinases in JNK signal transduction pathway. In conclusion, the present study provides experimental evidence to indicate existence of a novel pathway involving JNK signaling axis in regulation of DATS-induced ROS generation. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/16707465/c_Jun_NH_2__terminal_kinase_signaling_axis_regulates_diallyl_trisulfide_induced_generation_of_reactive_oxygen_species_and_cell_cycle_arrest_in_human_prostate_cancer_cells_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16707465 DB - PRIME DP - Unbound Medicine ER -