nonaarginine has been researched along with Neoplasms* in 3 studies
3 other study(ies) available for nonaarginine and Neoplasms
Article | Year |
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Self-Assembling Lipid-Peptide Hybrid Nanoparticles of Phospholipid-Nonaarginine Conjugates for Enhanced Delivery of Nucleic Acid Therapeutics.
Despite potential applications of nucleic acid therapeutics, the lack of effective delivery systems hinders their clinical application. To overcome the barriers to nucleic acid delivery, we previously reported nanoparticles using phospholipid-polyethylenimine conjugates. However, toxicity of polyethylenimine remains as a problematic issue. Herein, we proposed to substitute the polyethylenimine with arginine-rich peptide to obtain a less-toxic carrier system. Nonaarginine was conjugated to the distal end of phospholipid hydrocarbon chains leading to phospholipid-nonaarginine conjugates (PL9R) and then lipid-peptide hybrid nanoparticles carrying oligonucleotide therapeutics (hNP) were constructed by self-assembly process. The hNP were further modified with cell penetrating Tat peptide (T-hNP) to enhance cellular uptake. The PL9R was less cytotoxic, and the hNP showed high loading capacity and colloidal stability. The T-hNP showed higher cellular uptake and transfection efficiency and effective accumulation to tumor tissue and silencing effect in tumor bearing mice. Altogether, T-hNP could provide a promising nanocarrier for nucleic acid therapeutics. Topics: Animals; Cell-Penetrating Peptides; Drug Delivery Systems; Humans; Hydrocarbons; Mice; Nanoparticles; Neoplasms; Oligopeptides; Peptide Nucleic Acids; Phospholipids; Transfection; Xenograft Model Antitumor Assays | 2017 |
Overexpression of GRIM-19 in cancer cells suppresses STAT3-mediated signal transduction and cancer growth.
Constitutive activation of signal transducer and activator of transcription 3 (STAT3) is common in many human and murine cancer cells, and its activation leads to cellular transformation. STAT3 pathway inhibitors have been reported to suppress cancer growth. To investigate the antitumor effects of inhibiting the STAT3-mediated signaling cascade in the cancer microenvironment, using a molecular-targeting approach, we focused on the gene associated with retinoid-IFN-induced mortality 19 (GRIM-19). GRIM-19 has been reported to interact physically with STAT3 and inhibit STAT3-dependent signal transduction. We used the nona-arginine (R9)-protein transduction domain (R9-PTD) as a protein carrier to induce high levels of GRIM-19 expression in vitro and in vivo. We generated an R9-PTD-containing GRIM-19 fusion protein (rR9-GRIM19) and successfully induced overexpression in the cytoplasm of cancer cells. Analysis of the expression of downstream molecules of STAT3 confirmed that in vitro rR9-GRIM19 treatment of constitutively activated STAT3 (STAT3c) cancer cells significantly reduced STAT3-dependent transcription. Moreover, intratumoral injections of rR9-GRIM19 in STAT3c cancer-bearing mice significantly suppressed tumor growth. These results suggest that intratumoral injections of rR9-GRIM19 have potential as a novel anticancer therapy in STAT3c cancer due to their ability to inhibit STAT3-mediated signal transduction without major systemic side effects. Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Mice; NADH, NADPH Oxidoreductases; Neoplasms; Oligopeptides; Phosphorylation; Protein Structure, Tertiary; Recombinant Fusion Proteins; Signal Transduction; STAT3 Transcription Factor; Transcription, Genetic | 2010 |
Control of hypoxia-induced tumor cell adhesion by cytophilic human catalase.
Hypoxia-induced reactive oxygen species (ROS)-mediated expression of a variety of genes in endothelial cells has been suggested to be involved in abnormal cell adhesion. To prevent this by accelerated binding of catalase to endothelial cells, human catalase (hCAT), an enzyme catalyzing the decomposition of hydrogen peroxide, was fused with three repeats of arginine-glycine-aspartic acid peptide or nona arginine peptide at the C-terminal to obtain hCAT-(RGD)3 and hCAT-R9, respectively. Human CAT and its derivatives were expressed in yeast Pichia pastoris and purified. The specific activity and secondary structure of hCAT-(RGD)3 and hCAT-R9 were close to those of hCAT, but these derivatives showed higher binding to the mouse aortic vascular endothelial cell line MAEC than hCAT, indicating that they are cytophilic derivatives. Hypoxic treatment of MAEC increased the intracellular ROS level, the binding of mouse melanoma cells, and the activity of transcription factors, hypoxia inducible factor-1 and nuclear factor-kappaB. hCAT-(RGD)3 or hCAT-R9 efficiently inhibited these changes compared with hCAT. These results indicate that cytophilic hCAT-(RGD)3 and hCAT-R9 are effective in inhibiting hypoxia-induced tumor cell adhesion to endothelial cells. Topics: Animals; Catalase; Cats; Cell Adhesion; Cell Hypoxia; Endothelium, Vascular; Humans; Hydrogen Peroxide; Hypoxia-Inducible Factor 1; Mice; Neoplasms; NF-kappa B; Oligopeptides; Reactive Oxygen Species; Recombinant Fusion Proteins | 2009 |