title: Yessotoxin, a Marine Toxin, Exhibits Anti-Allergic and Anti-Tumoural Activities Inhibiting Melanoma Tumour Growth in a Preclinical Model.
abstract: Yessotoxins (YTXs) are a group of marine toxins produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. They may have medical interest due to their potential role as anti-allergic but also anti-cancer compounds. However, their biological activities remain poorly characterized. Here, we show that the small molecular compound YTX causes a slight but significant reduction of the ability of mast cells to degranulate. Strikingly, further examination revealed that YTX had a marked and selective cytotoxicity for the RBL-2H3 mast cell line inducing apoptosis, while primary bone marrow derived mast cells were highly resistant. In addition, YTX exhibited strong cytotoxicity against the human B-chronic lymphocytic leukaemia cell line MEC1 and the murine melanoma cell line B16F10. To analyse the potential role of YTX as an anti-cancer drug in vivo we used the well-established B16F10 melanoma preclinical mouse model. Our results demonstrate that a few local application of YTX around established tumours dramatically diminished tumour growth in the absence of any significant toxicity as determined by the absence of weight loss and haematological alterations. Our data support that YTX may have a minor role as an anti-allergic drug, but reveals an important potential for its use as an anti-cancer drug.
authors.affiliation: INSERM UMRS 1149, Paris, France.|Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, Lugo, Spain.|CNRS, Center de Recherche sur l'Inflammation, Equipe de Recherche Labellisée (ERL), Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, Paris, France.
authors.forename: Araceli
authors.initials: A
authors.lastname: Tobío
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, Lugo, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Alfonso
authors.affiliation: INSERM UMRS 1149, Paris, France.|CNRS, Center de Recherche sur l'Inflammation, Equipe de Recherche Labellisée (ERL), Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, Paris, France.
authors.forename: Iris
authors.initials: I
authors.lastname: Madera-Salcedo
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, Lugo, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Botana
authors.affiliation: INSERM UMRS 1149, Paris, France.|CNRS, Center de Recherche sur l'Inflammation, Equipe de Recherche Labellisée (ERL), Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, Paris, France.
authors.forename: Ulrich
authors.identifier: http://orcid.org/0000-0002-2661-2983
authors.initials: U
authors.lastname: Blank
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000009:adverse effects / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004141:Dinoflagellida / Q000737:chemistry; D006801:Humans; D008387:Marine Toxins / Q000009:adverse effects / Q000494:pharmacology; D051379:Mice; D008978:Mollusk Venoms; D035964:Oxocins / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D018926:Anti-Allergic Agents; D000970:Antineoplastic Agents; D008387:Marine Toxins; D008978:Mollusk Venoms; D035964:Oxocins; C066632:yessotoxin