Reactive oxygen species involved in sulforaphane-induced STAT3 inactivation and apoptosis in DU145 prostate cancer cells
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Signal transducer and activator of transcription factor 3 (STAT3) is a transcription factor that regulates various cellular processes such as proliferation, survival and angiogenesis in cancer cells. In the present study, we investigated the mechanisms whereby isothiocyanate sulforaphane (SFN) suppresses STAT3 activation in DU145 prostate cancer cells. SFN significantly inhibited SFN-inhibited STAT3 phosphorylation at Tyr705 as well as the deoxyribonucleic acid (DNA) binding capability in electrophoresis mobility shift assay (EMSA) in time- and concentration-dependent manner. SFN also abrogated the Janus activated kinase 2 (JAK2) phosphoraylation. In addition, SFN down-regulated STAT3-related gene products including Bcl-2, Bcl-xL, and cyclin D1 and vascular endothelial growth factor (VEGF), and inhibited the proliferation and induced apoptosis. Moreover, SFN mediated reactive oxygen species (ROS) production at the early time. Overall, these results demonstrate that ROS generation may be involved in the inhibition of JAK2/STAT3 activation and apoptosis in DU145 cells.
Keywordssulforaphane STAT3 apoptosis reactive oxygen species DU145
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