Marine toxins and the cytoskeleton: pectenotoxins, unusual macrolides that disrupt actin.
In recent years, many natural macrolactones have been found that display toxicity against the actin cytoskeleton. Pectenotoxins are macrolactones produced by species of the dinoflagellate genus Dinophysis. They were initially classified within the diarrheic shellfish poisoning group of toxins, because of their co-occurrence and biological origin, but mice toxicity assays demonstrated that pectenotoxins do not induce diarrheic symptoms. Intraperitoneal injection of pectenotoxins into mice produces high hepatotoxicity as the principal symptom, so the liver seems to be their target organ. Up to now, 15 pectenotoxin analogs have been discovered, with different toxicological potencies that are related to their structures. Now, it is generally accepted that the actin cytoskeleton is the principal molecular target of pectenotoxins. Although recent studies have demonstrated that pectenotoxins induce actin filament disruption by a capping effect, other kinds of activity, such as sequestration of actin, cannot be ruled out. All of the active analogs tested triggered disruption of the actin cytoskeleton and displayed potencies that correlated with their toxicity in mice. Moreover, pectenotoxins induce apoptosis to a higher degree in tumor cells than in normal cells of the same tissue. This fact opens the prospect of studying new chemotherapy agents and actin cytoskeleton dynamics with potential clinical applications.
Espiña
Begoña
B
Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain. begona.espina@usc.es
Rubiolo
Juan A
JA
D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology*; D004141:Dinoflagellida; D005663:Furans / Q000737:chemistry / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D018942:Macrolides; D008387:Marine Toxins / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008958:Models, Molecular; D011714:Pyrans / Q000737:chemistry / Q000633:toxicity*; D012758:Shellfish; D013329:Structure-Activity Relationship; D000095702:Polyether Toxins
D000199:Actins; D005663:Furans; D018942:Macrolides; D008387:Marine Toxins; D011714:Pyrans; C098380:pectenotoxin 2; D000095702:Polyether Toxins