ABSTRACT
We investigated the antioxidative properties of (2R,3S,2â³R,3â³R)-manniflavanone (MF) using in vitro assays and examined its effects on myogenesis and lactate-induced oxidative stress in C2C12 cells. MF was purified from Garcinia buchananii stem bark. H2O2 and oxygen radical absorbance capacity assays demonstrated that MF is a powerful antioxidant. This finding was supported by diphenylpicrylhydrazine radical scavenging activity of MF. MF was less cytotoxic to C2C12 cells compared to ascorbic acid and myricetin. Moreover, MF accelerated myotube formation in the differentiated C2C12 cells by up-regulating myogenic proteins such as MyoG and myosin heavy chain. Furthermore, MF rescued late differentiation of myoblast suppressed by lactate treatment and up-regulated the expression levels of Nrf2 in lactate-induced oxidative stress, indicating that MF stimulates antioxidative activity inside C2C12 cells. Collectively, MF is a potent antioxidant with a higher safety profile than ascorbic acid and myricetin. It reduces oxidative stress-induced delaying of skeletal muscle differentiation by scavenging reactive oxygen species and regulating myogenic proteins factors.
Subject(s)
Cell Proliferation/drug effects , Flavones/pharmacology , Garcinia/chemistry , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/cytology , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Protective Agents/pharmacology , Animals , Cell Differentiation/drug effects , Cell Line , Flavones/chemistry , Hydrogen Peroxide/toxicity , Mice , Muscle Fibers, Skeletal/cytology , Muscle Fibers, Skeletal/drug effects , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Myogenin/genetics , Myogenin/metabolism , Plant Bark/chemistry , Plant Extracts/chemistry , Protective Agents/chemistry , Up-Regulation/drug effectsABSTRACT
We present a novel method of radio frequency (RF)-mediated thermotherapy in tumors by remotely heating nickel (Ni)-gold (Au) core-shell nanowires (CSNWs). Ectopic pancreatic tumors were developed in nude mice to evaluate the thermotherapeutic effects on tumor progression. Tumor ablation was produced by RF-mediated thermotherapy via activation of the paramagnetic properties of the Ni-Au CSNWs. Histopathology demonstrated that heat generated by RF irradiation caused significant cellular death with pyknotic nuclei and nuclear fragmentation dispersed throughout the tumors. These preliminary results suggest that thermotherapy ablation induced via RF activation of nanowires provides a potential alternative therapy for cancer treatment.
Subject(s)
Hyperthermia, Induced/methods , Magnetite Nanoparticles/administration & dosage , Nanowires/administration & dosage , Pancreatic Neoplasms/therapy , Pulsed Radiofrequency Treatment/instrumentation , Pulsed Radiofrequency Treatment/methods , Animals , Cell Line, Tumor , Disease Progression , Gold/chemistry , Humans , Hyperthermia, Induced/instrumentation , Magnetite Nanoparticles/chemistry , Male , Mice , Mice, Nude , Nanowires/chemistry , Nickel/chemistry , Pancreatic Neoplasms/pathology , Xenograft Model Antitumor AssaysABSTRACT
Gold nanoparticles (AuNP) were conjugated with cysteine terminated KDEL (Lys-Asp-Glu-Leu) peptide and siRNA directed against NADPH Oxidase 4 (Nox4). Fluorescence microscopy analysis provided evidence of cytocellular retrograde transport pathways and sub-cellular colocalization of AuNP nanoconstructs in both undifferentiated C2C12 myoblasts and differentiated C2C12 myotubes. The cellular trafficking of AuNP nanoconstructs in undifferentiated myoblasts suggests stable and efficient transfection of siRNA as demonstrated by colocalization of AuNP-delivered KDEL and siRNA. The cellular uptake of AuNP nanoconstructs was more efficient than Lipofectamine mediated transfection in differentiated myotubes (P<0.05) compared to undifferentiated myoblasts, suggesting that AuNP nanoconstructs provide an efficient platform for siRNA delivery to differentiated myotubes. The localization of these nanoconstructs in undifferentiated myoblasts suggests that most of the siRNA was localized in the endoplasmic reticulum (ER) with a minimal distribution in the Golgi bodies suggesting that the ER is a primary localization site for AuNP-KDEL mediated delivery of nanoconstructs. FROM THE CLINICAL EDITOR: This team of investigators demonstrate that a delivery system composed of gold nanoparticle and KDEL based siRNA is superior to lipofectamine in delivering siRNA in differentiated myoblasts, paving the way to gene silencing methods in these cells for future therapeutic exploitation.