melitten and Cell-Transformation--Neoplastic

Melittin is the principal toxic component in the venom of the European honey bee Apis mellifera and is a cationic, hemolytic peptide. It is a small linear peptide composed of 26 amino acid residues in which the amino-terminal region is predominantly hydrophobic whereas the carboxy-terminal region is hydrophilic due to the presence of a stretch of positively charged amino acids. This amphiphilic property of melittin has resulted in melittin being used as a suitable model peptide for monitoring lipid-protein interactions in membranes. In this review, the solution and membrane properties of melittin are highlighted, with an emphasis on melittin-membrane interaction using biophysical approaches. The recent applications of melittin in various cellular processes are discussed.

Topics: Amino Acid Sequence; Animals; Cell Membrane; Cell Transformation, Neoplastic; Ion Channels; Leishmania; Melitten; Membrane Proteins; Models, Molecular; Molecular Sequence Data; Protein Folding; Protein Structure, Quaternary; Protein Structure, Secondary; Signal Transduction; Transfection

The prevalence of activated ras oncogenes in human primary tumors suggests a central role for this oncogene in human cancer. Despite its ubiquitous distribution, the biochemical role of the oncogene remains unclear, and hence attempts to control its activity have been frustrated. This study demonstrates the ability of melittin, a 26 amino acid, amphipathic peptide from bee venom, to specifically select against cells in culture that express high levels of the ras oncogene. Acquisition of resistance to increasing concentrations of melittin is accompanied by corresponding decreases in the levels of expression of the ras oncoprotein and the number of copies of the ras gene. This results in a concomitant reversion of transformed cells to a normal morphology in a strict dose-dependent manner. Melittin is a known activator of cellular phospholipase A2 (PLA2), and these results suggest an interrelationship between ras and PLA2. In addition these studies indicate that melittin preferentially hyperactivates PLA2 in ras oncogene-transformed cells, resulting in their selective destruction.

Topics: 3T3 Cells; Amino Acid Sequence; Animals; Cell Transformation, Neoplastic; Drug Resistance; Enzyme Activation; Genes, ras; Melitten; Mice; Molecular Sequence Data; Oncogene Protein p21(ras); Phospholipases A; Phospholipases A2

In a study performed on transformed (SGS/3A) and normal syngeneic rat cells (FG/2) to identify the molecular mechanisms which regulate cell adhesion and contact inhibition in cell transformation, we investigated the effects of tumor promoters on cell to cell adhesion of rat fibroblasts. As tumor promoters we used 12-tetradecanoyl-phorbole-13-acetate (TPA) and the melittin, a polypeptide from bee venom, both substances capable of stimulating the neoplastic transformation. The intercellular adhesion assay consists in determining the percent of single cells labeled with 3H-L-leucine adhering to a confluent monolayer of unlabeled cells at different incubation times. The increase of cell-cell adhesion caused by TPA and melittin confirms what we have constantly observed in other experiments, i.e. that neoplastic cells SGS/3A always have a higher intercellular adhesion capacity than corresponding normal syngenic cells FG/2. Since one of the effects of the tumor promoters is also induction of a reversible alteration of the cytoskeleton, it is likely that their action on intercellular adhesion is regulated by a mechanism analogous to that proposed for explaining the increased intercellular adhesion observed after treatment with antimicrotubular compounds.

Topics: Animals; Bee Venoms; Cell Adhesion; Cell Transformation, Neoplastic; Cells, Cultured; Fibroblasts; Melitten; Rats; Tetradecanoylphorbol Acetate

Griseofulvin, 12-O-tetradecanoyl phorbol-13-acetate, melittin, epidermal growth factor, vinblastine, cytochalasin B, podophyllotoxin, colcemid, and colchicine were unable to transform cells but could increase from 8- to 40-fold the frequency of cell transformation by polyoma virus. The 3T3-like cells were resting at confluence and were exposed to the drug only during the 1st week after viral infection. Griseofulvin, a tumor promoter, reduced or increased the frequency of transformation depending on the dose with which the infected cells were treated. The antitumor activity of tumor promoters is discussed.

Topics: Cell Line; Cell Transformation, Neoplastic; Cell Transformation, Viral; Colchicine; Cytochalasin B; Epidermal Growth Factor; Griseofulvin; Melitten; Mutagens; Podophyllotoxin; Polyomavirus; Tetradecanoylphorbol Acetate; Vinblastine

Topics: Amphotericin B; Biological Transport, Active; Blood; Blood Platelets; Cell Transformation, Neoplastic; Cells, Cultured; DNA; Fibroblasts; Growth Substances; Melitten; Monensin; Peptides; Platelet-Derived Growth Factor; Potassium; Rubidium; Sodium; Vasopressins

Topics: Animals; Arachidonic Acid; Bee Venoms; Bees; Cell Differentiation; Cell Division; Cell Line; Cell Line, Tumor; Cell Transformation, Neoplastic; Melanoma; Melitten; Mice; Prostaglandins; Tetradecanoylphorbol Acetate