Characterization of F-actin depolymerization as a major toxic event induced by pectenotoxin-6 in neuroblastoma cells.
Pectenotoxins are a group of marine toxins produced by dinoflagellates and formerly included within the group of diarrhetic shellfish poison or toxins (DSP or DST) because of their physico-chemical properties. However, toxicological data on pectenotoxins are still very scarce and its mechanism of action is largely unknown, but toxicity in laboratory animals has been demonstrated by intraperitoneal injection. In this report, we present results of in vitro toxicological assessment of pectenotoxin-6, a derivative of the parental toxin pectenotoxin-2 first isolated from toxic scallops. Results obtained demonstrate an specific time- and dose-dependent depolymerization of F-actin in neuroblastoma cells exposed to pectenotoxin-6 (half-maximal effect about 700 nM at 24 hr). The change in the state of polymerization of actin was not accompanied by other major effects on specific signal transduction pathways or cell survival rate. Pectenotoxin-6 does not modify cytosolic calcium levels either in a calcium containing or calcium-free medium in human lymphocytes. Only when capacitative calcium influx was first activated, the toxin addition significantly decreased the following calcium influx. In these cells, pectenotoxin-6 only modifies cAMP (adenosine 3',5'-cyclic monophosphate) levels in calcium-free conditions. In addition, no effect on cell attachment or apoptosis induction was observed at micromolar concentrations of pectenotoxin-6. Therefore, we conclude that cytoskeletal disruption is a key mechanism of PTX6-induced toxicity in eukaryotic cells.
Leira
Francisco
F
ANFACO-CECOPESCA, Campus Universitario de Vigo, 36310, Vigo, Spain. fleira@anfaco.es
Cabado
Ana G
AG
Vieytes
Mercedes R
MR
Roman
Yolanda
Y
Alfonso
Amparo
A
Botana
Luis M
LM
Yasumoto
Takeshi
T
Malaguti
Claudia
C
Rossini
Gian P
GP
D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D018942:Macrolides; D008387:Marine Toxins / Q000494:pharmacology*; D009447:Neuroblastoma; D011714:Pyrans / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000095702:Polyether Toxins
D000199:Actins; D002118:Calcium; D000242:Cyclic AMP; D005663:Furans; D018942:Macrolides; D008387:Marine Toxins; D011714:Pyrans; C114399:pectenotoxin 6; D000095702:Polyether Toxins