Delivery of a TNF-α-derived peptide by nanoparticles enhances its antitumor activity by inducing cell-cycle arrest and caspase-dependent apoptosis
Abstract
Prostate cancer is the second-most common malignancy of the male genitourinary system. TNF-α has attracted intense attention as a potential therapeutic agent against various cancers. However, its therapeutic application is restricted by short half life and severe toxic side-effects. In this study, we constructed a stable nanodrug, called TNF-α-derived polypeptide (P16)-conjugated, chitosan (CTS)-modified selenium nanoparticle (SC; SCP), which is composed of SC as a slow-release carrier conjugated to P16. SCP had significant inhibitory effects on multiple types of tumor cells, especially DU145 prostate cancer cells, but not on RWPE-1 normal human prostate epithelial cells. SCP could induce G0/G1 cell-cycle arrest and apoptosis in DU145 cells more effectively than could P16 and TNF-α. In DU145 xenograft tumor models, SCP exerted much stronger antitumor effects than P16 or estramustine (the clinical drug for prostate cancer) but caused fewer toxic side-effects. In addition, SCP significantly inhibited proliferation and accelerated apoptosis in DU145 xenograft tumors. Further mechanistic studies revealed that SCP exerted antitumor effects via activation of the p38 MAPK/JNK pathway, thus inducing G0/G1 cell-cycle arrest and caspase-...Continue Reading
References
Cyclophosphamide enhances TNF-alpha-induced apoptotic cell death in murine vascular endothelial cell
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