Induction of apoptosis by the marine sponge (Mycale) metabolites, mycalamide A and pateamine.
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.
Hood
K A
KA
School of Biological Sciences, Victoria University of Wellington, New Zealand.
West
L M
LM
Northcote
P T
PT
Berridge
M V
MV
Miller
J H
JH
D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D002470:Cell Survival; D004396:Coloring Agents / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology*; D005434:Flow Cytometry; D020128:Inhibitory Concentration 50; D018942:Macrolides; D008956:Models, Chemical; D011161:Porifera; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D011714:Pyrans / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*; D014343:Trypan Blue / Q000494:pharmacology
D017304:Annexin A5; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D018942:Macrolides; D011500:Protein Synthesis Inhibitors; D011714:Pyrans; D013778:Tetrazolium Salts; D013844:Thiazoles; C421324:pateamine A; D003561:Cytarabine; C059646:mycalamide A; D011691:Puromycin; D004247:DNA; D003513:Cycloheximide; C022616:thiazolyl blue; D014343:Trypan Blue