title: Azaspiracid-1 alters the E-cadherin pool in epithelial cells.
abstract: Azaspiracids cause severe damages in the epithelium of several organs. In this study we have investigated the effects of azaspiracid-1 (AZA-1) on two epithelial cell lines. Nanomolar concentrations of AZA-1 reduced MCF-7 cell proliferation and impaired cell-cell adhesion. AZA-1 altered the cellular pool of the adhesion molecule E-cadherin by inducing a dose- and time-dependent accumulation of an E-cadherin fragment (E-cadherin-related antigen [ECRA(100)]), with a concentration inducing the half-maximal effect (EC(50)) of 0.47nM. The immunological characterization of ECRA(100) revealed that it consists of an E-cadherin molecule lacking the intracellular domain, and these data showed that the effect induced by AZA-1 in MCF-7 cells is undistinguishable from that induced by yessotoxin (YTX) in the same experimental system. A comparison of toxin effects in MCF-7 and Caco 2 cells confirmed that the effects induced by AZA-1 and YTX are undistinguishable in these cells. Treatment of fibroblasts with AZA-1 did not affect the cellular pool of N-cadherin showing that the toxin effect is cadherin-specific. A comparison of the effects induced by AZA-1, YTX, and okadaic acid on F-actin and E-cadherin in MCF-7 and Caco 2 cells showed that 1nM AZA-1 did not cause significant changes in F-actin and that accumulation of ECRA(100) did not correlate with decreased levels of F-actin under our experimental conditions. Matching our results with those available in literature, we notice that, when molecular effects induced by AZA-1 and YTX have been studied in the same in vitro systems, experimental data show that they are undistinguishable in terms of sensitive cellular parameters, effective doses, and kinetics of responses in several cell lines. The possibility that azaspiracids and YTXs might share their molecular mechanism(s) of action in defined biological settings should be considered.
authors.affiliation: Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, I-41100 Modena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ronzitti
authors.forename: Philipp
authors.initials: P
authors.lastname: Hess
authors.forename: Nils
authors.initials: N
authors.lastname: Rehmann
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Rossini
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004988:Ethers, Cyclic / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008387:Marine Toxins / Q000302:isolation & purification / Q000633:toxicity*; D051379:Mice; D008978:Mollusk Venoms; D049880:Mytilus edulis / Q000737:chemistry; D035964:Oxocins / Q000633:toxicity; D013141:Spiro Compounds / Q000302:isolation & purification / Q000633:toxicity*; D013997:Time Factors; D000095702:Polyether Toxins
chemical_list: D000199:Actins; D015820:Cadherins; D004988:Ethers, Cyclic; D008387:Marine Toxins; D008978:Mollusk Venoms; D035964:Oxocins; D013141:Spiro Compounds; C406592:azaspiracid; D000095702:Polyether Toxins; C066632:yessotoxin