ABSTRACT
Twenty-two fragments of beta-actin and beta-actin-related protein were isolated from the acidic extracts of rat spleen tissue. beta-Actin fragments (75-90), (78-89), and (78-88), 0.01-1 microM, decreased live cell number of L929 murine tumor fibroblasts by 80-90%, with maximal cytotoxic effect of 30-40%. The fragments of (78-90) segment and the fragment of beta-actin-related protein (69-77) were less active (inhibitory effect up to 55%, cytotoxic-up to 25%).
Subject(s)
Acids/chemistry , Actins/isolation & purification , Actins/pharmacology , Neoplasms/pathology , Peptides/isolation & purification , Peptides/pharmacology , Spleen/metabolism , Actins/chemistry , Amino Acid Sequence , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Chromatography, Gel , Chromatography, High Pressure Liquid , Female , Mice , Molecular Sequence Data , Peptides/chemistry , Rats , Rats, Wistar , Tissue Extracts/chemistryABSTRACT
alpha-Hemoglobin fragments alpha-(133-141), alpha-(134-141), alpha-(135-141), alpha-(137-141), alpha-(134-140), alpha-(133-138), alpha-(134-140) and alpha-(137-138) stimulate L929 tumor cell proliferation, alpha-(134-141) being the most active. alpha-(134-141) stimulates proliferation of M3 melanoma cells, murine embryonic fibroblasts, primary cultures of red bone marrow and spleen cells. In L929 cells the effect of alpha-(134-141) is cell density independent; in M3 cells alpha-(137-141) and alpha-(134-141) are most active at density 10,000 cells/well (96 well plate) independently on FBS content.
Subject(s)
Cell Division/drug effects , Endorphins/pharmacology , Hemoglobins/chemistry , Peptide Fragments/pharmacology , Animals , Bone Marrow Cells/drug effects , Cell Count , Cell Survival/drug effects , Cells, Cultured , Culture Media, Serum-Free/pharmacology , Data Interpretation, Statistical , Dose-Response Relationship, Drug , Globins/chemistry , Mice , Oligopeptides/chemical synthesis , Oligopeptides/pharmacology , Spleen/cytology , Time Factors , Tumor Cells, Cultured/drug effectsABSTRACT
Hemorphins, i.e. endogenous fragments of beta-globin chain segment (32-41) LVVYPWTQRY(F) suppress the growth of transformed murine fibroblasts L929 cell culture, the effect is due to cytotoxicity and inhibition of cell proliferation. The contribution of cytotoxicity depends on the presence of Leu(32): VV-hemorphins, except VV-hemorphin-4, exhibit cytotoxicity significantly higher than respective LVV-hemorphins. Decrease of cell number induced by hemorphins depend on the extent of N- and C-terminal degradation of hemorphins: VV-hemorphins in most cases are more active than LVV-, V-hemorphins, and hemorphins. In the group of VV-hemorphins the activity of VV-hemorphin-5 (valorphin) is significantly higher than of VV-hemorphin-7, VV-hemorphin-6, and VV-hemorphin-4, meaning that the presence of C-terminal Gln is important for suppressing of cell number. The amino acid sequence VVYPWTQ corresponding to valorphin was identified as important for manifestation of the both cytotoxic and antiproliferative effects.