Lactone ring of pectenotoxins: a key factor for their activity on cytoskeletal dynamics.
BACKGROUND
Pectenotoxins are a group of natural products from marine origin that can accumulate in shellfish and intoxicate humans. Recently, novel homologues such as pectenotoxin-11 (PTX-11) and pectenotoxin-2 seco acid (PTX-2SA) have been identified. Their toxic potential towards experimental animals has been evaluated however their interaction with cellular systems is almost unknown. This is the first report showing (i) the biological activity of PTX-11 and PTX-2SA on actin cytoskeleton and morphology of living cells and (ii) the structure- activity relationship for this family of toxic compounds.


METHODS
Fluorescent phalloidin was utilized to quantify and visualize any modification in polymerized actin. Fluorescence values were obtained with laser-scanning cytometer and cells were imaged through confocal microscopy. For structure-activity evaluations, pectenotoxin-1 (PTX-1) and pectenotoxin-2 (PTX-2) was also analyzed.


RESULTS
Data showed that PTX-11 triggered a remarkable depolymerizing effect on actin cytoskeleton and also modifications in the shape of cells. In contrast, PTX-2SA did not evidence the same effects.


CONCLUSIONS
Our findings point out that (i) the actin cytoskeleton is a common target for PTX-11, PTX-2 and PTX-1, but not for PTX-2SA, and (ii) this difference in activity is related to the presence or absence of an intact lactone ring in their structures.
Ares
Isabel R
IR
Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
Louzao
M Carmen
MC
Espiña
Begoña
B
Vieytes
Mercedes R
MR
Miles
Christopher O
CO
Yasumoto
Takeshi
T
Botana
Luis  M
L
D000199:Actins / Q000187:drug effects*; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism*; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D018942:Macrolides; D008387:Marine Toxins / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D009447:Neuroblastoma; D011714:Pyrans / Q000737:chemistry / Q000494:pharmacology*; D000095702:Polyether Toxins
D000199:Actins; D003598:Cytoskeletal Proteins; D005663:Furans; D007783:Lactones; D018942:Macrolides; D008387:Marine Toxins; D011714:Pyrans; C420916:pectenotoxin-2-seco acid; D000095702:Polyether Toxins; C051905:pectenotoxin 1; C098380:pectenotoxin 2