Lactone Ring of Pectenotoxins: a Key Factor for their Activity on Cytoskeletal Dynamics

Abstract

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. Conclusion: 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.

Marine toxins and the cytoskeleton: pectenotoxins, unusual macrolides that disrupt actin

“…Control cells (A) and cells incubated for 4 h with 200 n m PTX‐11 (B), PTX‐2 (C), PTX‐1 (D) or PTX‐2 SA (E). Figure modified from [28]. Scale bar: 50 μm.…”

“…It has been shown that PTX-1, PTX-2, PTX-6 and PTX-11 disrupt the filamentous actin (F-actin) cytoskeleton in NRK-52E cells, rabbit enterocytes and neuroblastoma cells [28][29][30][31], and it is proposed that PTXs exert their toxicity by this mechanism.…”

Pectenotoxin‐2 represses telomerase activity in human leukemia cells through suppression of hTERT gene expression and Akt‐dependent hTERT phosphorylation

“…[20,21]. Previous studies have been also shown that PTX-2 may modify actin cytoskeletons due to its depolymerization through their binding sites with actin in vitro and in vivo [22,23]. In addition, this compound was reported to display selective and potent cytotoxicity against human lung, colon, and breast cancer cells [24,25].…”

Use of Biosensors as Alternatives to Current Regulatory Methods for Marine Biotoxins

“…Actually, it has been recently demonstrated that oral administration to mice does not cause any toxic effect, in spite of the toxicity induced by intraperitoneal administration [52,53]. The mechanism of action of pectenotoxin seems related to the disruption of the actin cytoskeleton observed in vitro [54-57]. The presence of pectenotoxins in seafood is regulated in several countries.…”