flavin-adenine-dinucleotide and Liver-Neoplasms

Topics: Adenosine Triphosphate; Animals; Azo Compounds; Carcinogens; Carcinoma, Hepatocellular; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Humans; Liver Neoplasms; Male; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Nucleotidyltransferases; Rats; Riboflavin; Riboflavin Deficiency

Topics: Binding Sites; Carcinoma, Hepatocellular; Centrifugation, Density Gradient; Chromatography, Gel; Escherichia coli; Flavin-Adenine Dinucleotide; Lactobacillus; Liver Neoplasms; NADP; Nucleotides; Oxidation-Reduction; Oxidoreductases; Protein Binding; Ribose; Sulfides; Tritium

Flavin adenine dinucleotide (FAD) is engaged in several metabolic diseases. Its main role is being a cofactor essential for the activity of many flavoproteins, which play a crucial role in electron transport pathways in living systems. The aim of this study was to apply a pegylated flavins formulation named FAD-PEG diacide complex as theranostic pathway in cancer therapy. For this purpose, a mouse liver cancer model induced by Hepa1-6 cells was used to evaluate the therapeutic efficacy of FAD (named NP1) and FAD-PEG diacide complex (named NP2). The cytokines were applied to screen the serum inflammatory factors, to establish the blood cell content of different groups of nude mice. The highlights follows that FAD formulations (NP1; NP2) significantly suppressed the tumor growth and reduced the tumor index without effects on the body weight of mice. Furthermore, NP2 significantly reduced the serum levels of cytokines IL-6, TNF-α and IL-12 (P70). The reported results provide the proof-of-concept for the synthesis of a smart adjuvant for liver cancer therapy and support their further development in the field of nanomedicine.

Topics: Animals; Antioxidants; Body Weight; Cell Line, Tumor; Cytokines; Flavin-Adenine Dinucleotide; Liver; Liver Neoplasms; Male; Mice; Mice, Nude; Polyethylene Glycols

Rat dimethylglycine dehydrogenase (Me2GlyDH) was used as model protein to study the biogenesis of a covalently flavinylated mitochondrial enzyme. Here we show that: 1) enzymatically active holoenzyme correlated with trypsin resistance of the protein; 2) folding of the reticulocyte lysate-translated protein into the trypsin-resistant, holoenzyme form was a slow process that was stimulated by the presence of the flavin cofactor and was more efficient at 15 degrees C than at 30 degrees C; 3) the mitochondrial presequence reduced the extent but did not prevent holoenzyme formation; 4) covalent attachment of FAD to the Me2GlyDH apoenzyme proceeded spontaneously and did not require a mitochondrial protein factor; 5) in vitro only the precursor, but not the mature form, of the protein was imported into isolated rat liver mitochondria; in vivo, in stably transfected HepG2 cells, both the precursor and the mature form were imported into the organelle; 6) holoenzyme formation in the cytoplasm did not prevent the translocation of the proteins into the mitochondria in vivo; and 7) lack of vitamin B2 in the tissue culture medium resulted in a reduced recovery of the precursor and the mature form of Me2GlyDH from cell mitochondria, suggesting a decreased efficiency of mitochondrial protein import.

Topics: Amino Acid Sequence; Animals; Base Sequence; Cell Line; Cloning, Molecular; Dimethylglycine Dehydrogenase; Flavin-Adenine Dinucleotide; Gene Expression; Hepatoblastoma; Humans; Kinetics; Liver Neoplasms; Methionine; Mitochondria, Liver; Mitochondrial Proteins; Molecular Sequence Data; Oligodeoxyribonucleotides; Oxidoreductases, N-Demethylating; Protein Biosynthesis; Protein Processing, Post-Translational; Rats; Recombinant Proteins; Sulfur Radioisotopes; Transfection; Tumor Cells, Cultured

Topics: Animals; Carcinoma, Hepatocellular; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Liver; Liver Neoplasms; Male; Neoplasms, Experimental; Nucleotidyltransferases; Rats; Riboflavin; Riboflavin Deficiency

Topics: Animals; Aspartate Aminotransferases; Carcinoma, Hepatocellular; Chemical and Drug Induced Liver Injury; Electron Spin Resonance Spectroscopy; Flavin-Adenine Dinucleotide; Infrared Rays; Isoenzymes; L-Lactate Dehydrogenase; Lipoproteins; Liver; Liver Diseases; Liver Neoplasms; Mitomycins; Neoplasms, Experimental; p-Dimethylaminoazobenzene; Peroxides; Rats; Riboflavin

Topics: Animals; Flavin-Adenine Dinucleotide; In Vitro Techniques; Liver Neoplasms; Neoplasms, Experimental; Rats; Riboflavin

Topics: Adult; Female; Flavin-Adenine Dinucleotide; Humans; Liver Diseases; Liver Neoplasms; Male; Riboflavin

Topics: Animals; Carcinogens; Flavin-Adenine Dinucleotide; Flavins; Hydrocortisone; Liver; Liver Neoplasms; Oxidoreductases; p-Dimethylaminoazobenzene; Rats