pateamine-a and thiazolyl-blue

The marine sponge metabolites mycalamide A (mycalamide) and pateamine are extremely cytotoxic. While mycalamide has been shown to inhibit protein synthesis, the mechanism by which these compounds induce cell death is unknown. Using DNA laddering, Annexin-V staining, and morphological analysis, we demonstrate that both metabolites induce apoptosis in several different cell lines. Furthermore, both mycalamide and pateamine were more potent inducers of apoptosis in the 32D myeloid cell line after transformation with either the ras or bcr-abl oncogenes. This increased sensitivity was also observed in response to the protein synthesis inhibitors cycloheximide and puromycin, and cytosine-beta-D-arabinofuranoside (Ara-C), an inducer of DNA damage. We propose, therefore, that in 32D cells where Ras signalling has been altered either by constitutive expression of oncogenic ras or by Bcr/abl-mediated perturbation of upstream signalling events, increased susceptibility to apoptosis by a range of stimuli is conferred.

Topics: Animals; Annexin A5; Apoptosis; Cell Survival; Coloring Agents; Cycloheximide; Cytarabine; DNA; DNA Damage; Electrophoresis, Agar Gel; Enzyme Inhibitors; Epoxy Compounds; Flow Cytometry; Inhibitory Concentration 50; Macrolides; Models, Chemical; Porifera; Protein Synthesis Inhibitors; Puromycin; Pyrans; Tetrazolium Salts; Thiazoles; Trypan Blue